2.Correlation between blood pressure indexes and prognosis in sepsis patients: a cohort study based on MIMIC-III database.
Xiaobin LIU ; Yu ZHAO ; Yingyi QIN ; Qimin MA ; Yusong WANG ; Zuquan WENG ; Feng ZHU
Chinese Critical Care Medicine 2023;35(6):578-585
		                        		
		                        			OBJECTIVE:
		                        			To investigate the correlation between early-stage blood pressure indexes and prognosis in sepsis patients.
		                        		
		                        			METHODS:
		                        			A retrospective cohort study was conducted on the medical records of patients diagnosed with sepsis from 2001 to 2012 in the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients were divided into survival group and death group according to the 28-day prognosis. General data of patients and heart rate (HR) and blood pressure at admission to ICU and within 24 hours after admission were collected. The blood pressure indexes including the maximum, median and mean value of systolic index, diastolic index and mean arterial pressure (MAP) index were calculated. The data were randomly divided into training set and validation set (4 : 1). Univariate Logistic regression analysis was used to screen covariates, and multivariate Logistic stepwise regression models were further developed. Model 1 (including HR, blood pressure, and blood pressure index related variables with P < 0.1 and other variables with P < 0.05) and Model 2 (including HR, blood pressure, and blood pressure index related variables with P < 0.1) were developed respectively. The receiver operator characteristic curve (ROC curve), precision recall curve (PRC) and decision curve analysis (DCA) curve were used to evaluate the quality of the two models, and the influencing factors of the prognosis of sepsis patients were analyzed. Finally, nomogram model was developed according to the better model and effectiveness of it was evaluated.
		                        		
		                        			RESULTS:
		                        			A total of 11 559 sepsis patients were included in the study, with 10 012 patients in the survival group and 1 547 patients in the death group. There were significant differences in age, survival time, Elixhauser comorbidity score and other 46 variables between the two groups (all P < 0.05). Thirty-seven variables were preliminarily screened by univariate Logistic regression analysis. After multivariate Logistic stepwise regression model screening, among the indicators related to HR, blood pressure and blood pressure index, the HR at admission to ICU [odds ratio (OR) = 0.992, 95% confidence interval (95%CI) was 0.988-0.997] and the maximum HR (OR = 1.006, 95%CI was 1.001-1.011), maximum MAP index (OR = 1.620, 95%CI was 1.244-2.126), mean diastolic index (OR = 0.283, 95%CI was 0.091-0.856), median systolic index (OR = 2.149, 95%CI was 0.805-4.461), median diastolic index (OR = 3.986, 95%CI was 1.376-11.758) were selected (all P < 0.1). There were 14 other variables with P < 0.05, including age, Elixhauser comorbidity score, continuous renal replacement therapy (CRRT), use of ventilator, sedation and analgesia, norepinephrine, norepinephrine, highest serum creatinine (SCr), maximum blood urea nitrogen (BUN), highest prothrombin time (PT), highest activated partial thromboplastin time (APTT), lowest platelet count (PLT), highest white blood cell count (WBC), minimum hemoglobin (Hb). The ROC curve showed that the area under the curve (AUC) of Model 1 and Model 2 were 0.769 and 0.637, respectively, indicating that model 1 had higher prediction accuracy. The PRC curve showed that the AUC of Model 1 and Model 2 were 0.381 and 0.240, respectively, indicating that Model 1 had a better effect. The DCA curve showed that when the threshold was 0-0.8 (the probability of death was 0-80%), the net benefit rate of Model 1 was higher than that of Model 2. The calibration curve showed that the prediction effect of the nomogram model developed according to Model 1 was in good agreement with the actual outcome. The Bootstrap verification results showed that the nomogram model was consistent with the above results and had good prediction effects.
		                        		
		                        			CONCLUSIONS
		                        			The nomogram model constructed has good prediction effects on the 28-day prognosis in sepsis patients, and the blood pressure indexes are important predictors in the model.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Blood Pressure
		                        			;
		                        		
		                        			Intensive Care Units
		                        			;
		                        		
		                        			ROC Curve
		                        			;
		                        		
		                        			Sepsis/diagnosis*
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Critical Care
		                        			;
		                        		
		                        			Norepinephrine
		                        			
		                        		
		                        	
3.Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats.
Ming-Min PAN ; Qi-Yang WANG ; Jun-Lin HOU ; Tong ZHANG ; Yu JIANG ; Li-Ping YANG
Chinese Acupuncture & Moxibustion 2023;43(2):191-196
		                        		
		                        			OBJECTIVE:
		                        			To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.
		                        		
		                        			METHODS:
		                        			Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.
		                        		
		                        			RESULTS:
		                        			Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.
		                        		
		                        			CONCLUSION
		                        			Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.
		                        		
		                        		
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Moxibustion
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Rats, Wistar
		                        			;
		                        		
		                        			Serotonin
		                        			;
		                        		
		                        			Hippocampus
		                        			;
		                        		
		                        			Dopamine
		                        			;
		                        		
		                        			Norepinephrine
		                        			;
		                        		
		                        			Neurotransmitter Agents
		                        			
		                        		
		                        	
4.Effect of transcutaneous acupoint electrical stimulation at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy.
Yi DING ; Sheng-Yong SU ; Ya-Li LIN ; Yi-Tong WEI ; Jun-Dan SHI ; Si-Li GAO ; Jin-Yi ZHUO ; Yuan-Chun CAI
Chinese Acupuncture & Moxibustion 2023;43(3):282-286
		                        		
		                        			OBJECTIVE:
		                        			To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy.
		                        		
		                        			METHODS:
		                        			A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (PETCO2) and minimum value of oxygen saturation (SpO2) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T0), at the start of surgery (T1), thoracic exploration (T2) and lobectomy (T3), as well as 30 min (T4) and 60 min (T5) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups.
		                        		
		                        			RESULTS:
		                        			The maximum value of PETCO2, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO2 in the observation group was higher than that of the control group (P < 0.01). At T1-T5, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01).
		                        		
		                        			CONCLUSION
		                        			For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Acupuncture Points
		                        			;
		                        		
		                        			Carbon Dioxide
		                        			;
		                        		
		                        			Flatulence
		                        			;
		                        		
		                        			Propofol
		                        			;
		                        		
		                        			Remifentanil
		                        			;
		                        		
		                        			Anesthesia, General
		                        			;
		                        		
		                        			Nausea
		                        			;
		                        		
		                        			Norepinephrine
		                        			;
		                        		
		                        			Electric Stimulation
		                        			
		                        		
		                        	
5.Establishment of a Rat Model of Hypotension Induced by Reserpine.
Xuan ZHANG ; Ci WANG ; Ze-Yu ZHANG ; Pei-Pei ZHANG ; Qiu'an REN ; Xian-Liang WANG ; Jing-Yuan MAO
Acta Academiae Medicinae Sinicae 2023;45(4):533-540
		                        		
		                        			
		                        			Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Reserpine
		                        			;
		                        		
		                        			Dopamine
		                        			;
		                        		
		                        			Rats, Wistar
		                        			;
		                        		
		                        			Hypotension/chemically induced*
		                        			;
		                        		
		                        			Norepinephrine
		                        			
		                        		
		                        	
6.Clinical effectiveness of fecal microbiota transplantation combined with nutritional support and psychological intervention in patients with "Tetralogy of Tongji".
Zhi Liang LIN ; Ju Bao LU ; Qi Yi CHEN ; Jia Qu CUI ; Chen YE ; Hong Liang TIAN ; Huan Long QIN ; Ning LI
Chinese Journal of Gastrointestinal Surgery 2022;25(9):784-791
		                        		
		                        			
		                        			Objective: To summarize and analyze the clinical effect of fecal microbiota transplantation (FMT) combined with nutritional support and psychotherapy in patients with "Tetralogy of Tongji" (comprising chronic gastrointestinal dysfunction, mental and psychological disorders, malnutrition, and endocrine disorders). Methods: A longitudinal study was conducted. The inclusion criteria were as follows: (1) patients were under 70 years of age; (2) patients exhibited chronic gastrointestinal dysfunction (in accordance with the Rome IV diagnostic criteria for irritable bowel syndrome ie. chronic functional constipation, diarrhea, abdominal pain and abdominal distention) with onset occurring more than one year previously; (3) patients exhibited malnutrition (body mass index ≤ 18.5 kg/m2); (4) patients exhibited depression, anxiety, or state as diagnosed by a psychologist using the Hamilton anxiety rating scale (HAMA) and the Hamilton depression scale (HAMD); (5) patients were women of childbearing age with amenorrhea or menstrual disorder with a duration ≥6 months. Patients were excluded if they exhibited gastrointestinal bleeding, short bowel syndrome, radiation-induced intestinal injury, intestinal obstruction or inflammatory bowel disease, recurrent/metastatic tumors, systemic infectious diseases, life-threatening systemic comorbidities, intorlerate to nasojejunal, percutaneous gastrostomy / jejunostomy or FMT. The clinical data of 43 patients at Shanghai Tenth People's Hospital exhibiting the "Tetralogy of Tongji" and who received microflora transplantation combined with nutritional support and psychotherapy from June 2017 to June 2021 was prospectively collected. There were 12 males and 31 females with a mean age of 35.2±16.7 years. All 43 patients had chronic gastrointestinal dysfunction. Of these, 24 patients had depression and 19 had anxiety. There were 26 women of reproductive age, including 13 cases of menstrual disorder and 9 cases of amenorrhea. The treatment intervention was a combination of FMT (microflora solution or microflora capsule), nutritional support (enteral nutrition) and psychological intervention. The following were assessed before treatment and 1, 3, 6 months after treatment: (1) gastrointestinal function was assessed using the gastrointestinal symptoms rating scale (GSRS), where a higher score is indicative of more serious gastrointestinal symptoms, and the gastrointestinal quality of life index (GIQLI), where a higher score is indicative of higher quality of life; (2) psychological status was assessed using HAMA and HAMD scores, where a lower score is indicative of reduced severity of anxiety or depression symptoms, respectively; (3) nutritional status was assessed by measurements of total blood protein, albumin, fibrinogen and prealbumin, as well as measurements of body mass and body mass index (BMI); (4) neuroendocrine function was assessed by measurement of blood levels of cortisol, dopamine and noradrenaline, as well as menstruation in women of reproductive age. Results: The follow-up rates at 1, 3 and 6 months after treatment were 90.7% (39/43), 72.1% (31/43) and 55.8% (24/43), respectively. The total effective rate for chronic gastrointestinal dysfunction was 81.4% (35/43), of which the average GSRS score decreased from 29.35±3.56 before treatment to 18.25±2.56 in the sixth month (P<0.001). The average GIQLI score increased from 56.23±10.34 before treatment to 91.04±20.39 in the sixth month (P<0.001). All patients had malnutrition before treatment. After 6 months, their body weight had increased from 40.61±8.88 kg to 50.45±6.23 kg (P<0.001), and BMI had increased from 15.17±1.87 kg/m2 to 19.58±1.42 kg/m2 (P<0.001). The average total protein level was 60.99± 5.99 g/L before treatment. After 6 months, this had increased to 64.21±4.23 g/L (F=2.715, P=0.022). The average prealbumin level increased from 150.14±56.04 mg/L before treatment to 258.17±86.94 mg/L after 6 months (F=15.124, P<0.001). In this study, 24 patients with depression/depressed state were included. After treatment, the average HAMD score in these patients decreased from 22.79±6.63 before treatment to 9.92±7.24 after 6 months (P<0.001). There were 19 patients with anxiety disorder/anxiety state. After treatment, the average HAMA score in these patients decreased from 17.15±4.34 before treatment to 7.73±4.10 after 6 months (P<0.001). Observing the endocrine efficacy of 26 women of childbearing age, it was found that the effective rate of this treatment on endocrine regulation was 69.2% (18/26). Although there was no significant change in blood cortisol levels after 6 months, average blood dopamine levels decreased from 32.91±10.65 nmol/L before treatment to 13.02±5.58 nmol/L after 6 months (P<0.001). Average blood norepinephrine levels decreased from 49.75±15.23 ng/L before treatment to 19.21±9.58 ng/L after 6 months (P<0.001). Conclusion: The strategy of FMT combined with nutritional support and psychological intervention is effective in improving the symptoms of the "Tetralogy of Tongji".
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Amenorrhea
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Constipation
		                        			;
		                        		
		                        			Dopamine
		                        			;
		                        		
		                        			Fecal Microbiota Transplantation
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fibrinogen
		                        			;
		                        		
		                        			Gastrointestinal Diseases
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hydrocortisone
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Longitudinal Studies
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Malnutrition
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Norepinephrine
		                        			;
		                        		
		                        			Nutritional Support
		                        			;
		                        		
		                        			Prealbumin
		                        			;
		                        		
		                        			Psychosocial Intervention
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
7.β-arrestin2 recruitment by β-adrenergic receptor agonists and antagonists.
Yi-Ran WANG ; De-Qin CHENG ; Lan MA ; Xing LIU
Acta Physiologica Sinica 2022;74(6):993-1004
		                        		
		                        			
		                        			A large number of β-adrenergic receptor (β-AR) agonists and antagonists are widely used in the treatment of cardiovascular diseases and other diseases. Nonetheless, it remains unclear whether these commonly used β-AR drugs can activate downstream β- arrestin-biased signaling pathways. The objective of this study was to investigate β-arrestin2 recruitment effects of β-AR agonists and antagonists that were commonly used in clinical practice. We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene. Upon activation of β-AR by a β-AR ligand, β-arrestin2 was recruited to the C terminus of the receptor, followed by cleavage of the G protein-coupled receptors (GPCRs) fusion protein at the TEV protease-cleavage site. The cleavage resulted in the release of tTA, which, after being transported to the nucleus, activated transcription of the luciferase reporter gene. The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR. β2-AR selective agonists procaterol and salbutamol promoted β-arrestin2 recruitment at β2-AR. β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			beta-Arrestin 2/metabolism*
		                        			;
		                        		
		                        			HEK293 Cells
		                        			;
		                        		
		                        			Adrenergic beta-Agonists/pharmacology*
		                        			;
		                        		
		                        			Isoproterenol/pharmacology*
		                        			;
		                        		
		                        			Receptors, Adrenergic, beta-2/metabolism*
		                        			;
		                        		
		                        			Norepinephrine/pharmacology*
		                        			
		                        		
		                        	
8.Dexmedetomidine improves alcohol withdrawal symptom via activating α2 adrenergic receptor in rat hippocampus.
Ting ZENG ; Hong-Yan ZHANG ; Xin ZHAO ; Yan LIU ; Yan-Zhong GUAN
Acta Physiologica Sinica 2022;74(4):541-547
		                        		
		                        			
		                        			The purpose of this study was to investigate the effects of α2 adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism, so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome (AWS). Adult Sprague-Dawley (SD) male rats were orally administered with 6% aqueous alcohol continuously for 28 d to establish alcohol drinking model, and then stopped drinking to induce AWS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of norepinephrine (NE) in the locus coeruleus and hippocampus of rats. Dexmedetomidine (5, 10, and 20 μg/kg) was intraperitoneally injected respectively when the rats showed significant AWS. In some rats, α2 adrenergic receptor antagonist yohimbine was injected into hippocampus in advance. The results showed that, compared with the control group, the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking. The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group. Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group, while yohimbine could reverse these effects of dexmedetomidine. These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activating α2 adrenergic receptor.
		                        		
		                        		
		                        		
		                        			Adrenergic alpha-2 Receptor Agonists/therapeutic use*
		                        			;
		                        		
		                        			Alcoholism/drug therapy*
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Dexmedetomidine/therapeutic use*
		                        			;
		                        		
		                        			Hippocampus/metabolism*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Norepinephrine
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Receptors, Adrenergic, alpha-2/metabolism*
		                        			;
		                        		
		                        			Substance Withdrawal Syndrome/drug therapy*
		                        			;
		                        		
		                        			Yohimbine/pharmacology*
		                        			
		                        		
		                        	
9.Effect of Rehmanniae Radix on depression-like behavior and hippocampal monoamine neurotransmitters of chronic unpredictable mild stress model rats.
Ping TIAN ; Wei ZHANG ; Kai-Yan LI ; Hong-Wei LI ; Kai MA ; De-En HAN
China Journal of Chinese Materia Medica 2022;47(17):4691-4697
		                        		
		                        			
		                        			To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.
		                        		
		                        		
		                        		
		                        			3,4-Dihydroxyphenylacetic Acid/pharmacology*
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Antidepressive Agents/therapeutic use*
		                        			;
		                        		
		                        			Chromatography, Liquid
		                        			;
		                        		
		                        			Depression/drug therapy*
		                        			;
		                        		
		                        			Disease Models, Animal
		                        			;
		                        		
		                        			Dopamine
		                        			;
		                        		
		                        			Eosine Yellowish-(YS)/pharmacology*
		                        			;
		                        		
		                        			Hematoxylin/pharmacology*
		                        			;
		                        		
		                        			Hippocampus/metabolism*
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		                        			Homovanillic Acid/pharmacology*
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		                        			Hydroxyindoleacetic Acid/metabolism*
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		                        			Methoxyhydroxyphenylglycol/pharmacology*
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		                        			Monoamine Oxidase/metabolism*
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		                        			Neurotransmitter Agents/metabolism*
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		                        			Norepinephrine/pharmacology*
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		                        			Plant Extracts
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		                        			Rats
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		                        			Rehmannia/chemistry*
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		                        			Serotonin/metabolism*
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		                        			Serotonin Plasma Membrane Transport Proteins/pharmacology*
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		                        			Stress, Psychological/metabolism*
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		                        			Tandem Mass Spectrometry
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		                        			Tryptophan Hydroxylase/metabolism*
		                        			
		                        		
		                        	
10.Noradrenaline modulates the spontaneous firing activities of Purkinje cells via α2-adrenergic receptor in mouse cerebellar cortex.
Xu-Dong ZHANG ; Li-Fei WANG ; Fang-Ling XUAN ; De-Lai QIU ; Bin-Bin ZHANG ; Chun-Ping CHU
Acta Physiologica Sinica 2022;74(3):359-369
		                        		
		                        			
		                        			Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABAA receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABAA receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.
		                        		
		                        		
		                        		
		                        			Action Potentials/physiology*
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		                        			Animals
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		                        			Cerebellar Cortex/metabolism*
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		                        			Cerebellum/metabolism*
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		                        			Mice
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		                        			Norepinephrine/pharmacology*
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		                        			Purkinje Cells/metabolism*
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		                        			Receptors, Adrenergic, alpha-2/metabolism*
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		                        			Receptors, GABA-A/metabolism*
		                        			
		                        		
		                        	
            
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