1.Effect and its mechanism of esketamine on anxiety and depression in mice
Jingwen Zhou ; Yuanhai Li ; Gaolin Qiu ; Wen Cai ; Yuanyuan Zhao ; Xiaoqiong Xia
Acta Universitatis Medicinalis Anhui 2024;59(1):106-110
Objective :
To explore the effect of esketamine on anxiety-depressive-like behavior in mice and its rela- tionship with inflammation.
Methods :
SPF grade healthy adult male C57BL/6J mice,weighing 20 -24 g,were used in the exprement.The random number table method was used to divide into 5 groups (n = 8) : control group ( Con group) ,esketamine group (ESK group) ,model group ( LPS group) ,model + esketamine prevention group (LPS + ESK1 group) and model + esketamine treatment group ( LPS + ESK2 group) .An inflammation-induced anxiety-depression model was prepared by intraperitoneal injection of LPS 0. 83 mg / kg.The ESK group was injec- ted with esketamine 10 mg / kg ; LPS group was injected with LPS 0. 83 mg / kg ; LPS + ESK1 group was injected with LPS 0. 83 mg / kg before 24 hours intraperitoneal injection of esketamine 10 mg / kg ; and the LPS + ESK2 group was injected with LPS 0. 83 mg / kg and 30 minutes later with esketamine 10 mg / kg.24 h after intraperitoneal injec- tion of LPS,the anxiety-depression-like behaviors of mice were measured using behavioral experiments.At the end of behavioral experiments,the spleen was taken immediately ; hippocampal tissues were taken and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-1 β (IL-1 β) ,tumor necrosis factor al- pha (TNF-α) and interleukin 6 (IL-6) and neuronal pathological changes in hippocampal tissues were observed by HE staining.
Results :
Compared with the Con group,mice in the LPS group showed increased anxiety and depres- sion-like behavior (P<0. 05) ,increased spleen weight / body weight (P <0. 05 ) ,increased hippocampal tissue concentrations of IL-1 β , TNF-α and IL-6 (P<0. 05) ,and increased neuronal degeneration necrosis,there was no statistically significant difference in these indicators in the ESK group compared with the Con group.Compared with the LPS group,mice in the LPS + ESK1 and LPS + ESK2 groups showed reduced anxiety-depression-like behavior (P<0. 05) ,decreased splenic weight / body weight (P <0. 05) ,hippocampal tissue IL-1 β , TNF-α , IL- 6 con- centrations were reduced (P<0. 05) ,and neuronal degeneration necrosis was reduced.Compared with the LPS + ESK1 group,the LPS + ESK2 group showed an increase in the distance travelled in the central area of the open field experiment and the distance into the open arm of the elevated cross maze experiment (P<0. 05) ,a decrease in IL-6 and TNF-α concentrations (P<0. 05) ,and a reduction in the degree of neuronal damage.
Conclusion
Esketamine ameliorates LPS-induced anxiety-depression-like behavior and neuronal damage in mice by a mechanism that may be related to reduced inflammation.
2.Effects of remimazolam combined with esketamine on anaesthetic effect and mental symptom in pu-erperae undergoing cesarean section
Xianhong SHAO ; Bolang ZHU ; Chunhui WANG ; Jun CHANG ; Yuanhai LI
The Journal of Clinical Anesthesiology 2024;40(7):719-722
Objective To investigate the effect of remimazolam combined with esmketamine adjuvant medicines on anaesthetic effect and mental symptom in puerperae undergoing cesarean section.Methods Ninety-six full-term puerperae during cesarean section under combined spinal-epidural anesthe-sia,aged 24-38 years,BMI 24-35 kg/m2,ASA physical status Ⅰ or Ⅱ.All the puerperae were divided into three groups using random number table:remimazolam combined with esketamine group(group RK),esketamine group(group K),and control group(group C),32 puerperae in each group.After the delivery of the fetus,puerperae in group RK were given intravenous injection of remimazolam 0.1 mg/kg,and then intravenous pumping of estaketamine 0.25 mg/kg which was diluted to 20 ml with normal saline(finished in 30 minutes),puerperae in group K were given intravenous pumping of estaketamine 0.25 mg/kg which was diluted to 20 ml with normal saline(finished in 30 minutes),puerperae in group C were given the same dose of normal saline.All puerperae were given PCIA after operation.The anesthetic effect from the fetus de-livery to the end of operation were recorded(grade Ⅰ,no pain;grade Ⅱ,slight pain;grade Ⅲ,with sig-nificant pain).The adverse reactions such as hypertension,tachycardia,and mental symptoms(nystagmus,dizziness,nightmares and hallucinations)during surgery were recorded.The score of Edinburgh postpartum depression scale(EPDS)and incidence of postpartum depression(PPD)at 1 week and 4 weeks after sur-gery were recorded.Results Compared with group C,the proportion of grade Ⅰ anesthetic effect in groups,RK and K was significantly increased,and the proportion of grade Ⅲ anesthetic effect was signifi-cantly decreased(P<0.05),the EPDS score and the incidence of PPD were significantly decreased at 1 week and 4 weeks after surgery(P<0.05).Compared with group K,the incidence of mental symptoms during surgery in group RK was significantly decreased(P<0.05),EPDS score was significantly decreased at 1 week and 4 weeks after surgery(P<0.05).There were no significant differences in the in-cidences of hypertension,tachycardia between the three groups.Conclusion Remimazolam combined with esketamine for cesarean section can improve the anesthetic effect during surgery,reduce the incidence of in-traoperative mental sympton,decrease the postpartum EPDS score,optimize postpartum depression.
3.Effect of Esketamine on Early Negative Postoperative Behavioural Occurrence After Pediatric Concealed Penis Correction
Huan ZHANG ; Yingying SUN ; Yin XIA ; Yuanhai LI
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):835-843
[Objective]To investigate the effect of esketamine pretreatment on early negative postoperative behavioural occurrence after pediatric concealed penis correction.[Methods]A total of 88 children,aged 4-10 years old,of American Society of Anesthesiologists physical status Ⅰ-Ⅱ,undergoing pediatric cryptorchid penis correction operation within 1 hour,were randomly divided into the esketamine group(Group E,n=44)and the control group(Group C,n=44)according to the computer-generated random numeral order.Esketamine was infused intravenously at a dose of 0.5 mg/kg 20 minutes before entering the operating room in Group E,while equal volume of normal saline was given instead of esketamine in group C.General anesthesia with laryngeal mask and inhalation anesthesia was used in both groups.The anxiety level of children was evaluated by modified Yale Preoperative Anxiety Scale(m-YPAS)on the day before surgery and before entering operating room on the day of the operation.The induction compliance level of children was evaluated by the Induction Compliance Checklist(ICC).Heart rate(HR)and mean arterial pressure(MAP)were recorded before the induction of anesthesia(T0),immediately after the induction(T1),the beginning of the operation(T2),the time of admission to the PACU(T3),10 min after the PACU(T4),and before discharge from PACU(T5).Paediatric Anaesthesia Awakening Delirium Scale(PAED)and Pain Behavioural Assessment Scale(FLACC)scores were performed during awakening.A volume of 3 mL of peripheral venous blood was collected on the first preoperative day as well as the first postoperative day,and the levels of monocyte chemotactic protein 1(MCP-1),cortisol and epinephrine were measured.The Postoperative Behavioural Questionnaire(PHBQ)questionnaire was recorded on postoperative days 3 and 7 for all children.[Results]The incidence of NPOBCs on postoperative days 3 and 7 was significantly lower in Group E compared with that of Group C(31.8%vs.63.6%,P<0.05;18.2%vs.40.9%,P<0.05).The incidence of separation anxiety,sleep anxiety,and eating disorders in the PHBQ on postoperative day 3 was significantly lower in Group E than in Group C.The difference was statistically significant(P<0.05);there was no statistically significant difference between the two groups when comparing the incidence of overall anxiety,aggression,and apathetic withdrawal(P>0.05).On postoperative day 7,the incidence of all indicators in the PHBQ was not statistically different between the 2 groups(P>0.05).Compared with Group C,postoperative MCP-1 was significantly lower in Group E,and the difference was statistically significant(P<0.05);whereas for epinephrine and cortisol levels,there was no statistically significant difference between the 2 groups(P>0.05).Multivariable logistic regression analysis suggested that the possible risk factors for NPOBCs after pediatric concealed penis correction included the m-YPAS score[OR=1.152,95%CI(1.083,1.226);P=0.000],and the use of esketamine[OR=0.223,95%CI(0.062,0.803);P=0.022].The AUC under the ROC curve of m-YPAS and the use of esketamine as two predictors of the occurrence of NPOBCs were 0.918[P<0.001,95%CI(0.849,0.988)]and 0.659[P=0.010,95%CI(0.544,0.774)],respectively.There was no statistically significant difference in PAED scores and FLACC scores between the two groups in the PACU(P>0.05).[Conclusion]Esketamine pretreatment can reduce the incidence of NPOBCs in children undergoing concealed penis correction,which may be associated with a reduction in postoperative MCP-1,without an increase in perioperative adverse events and with a high safety profile.
4.Protective effect and mechanisms of remimazolam on cognitive function in septic mice
Wen Cai ; Gaolin Qiu ; Yuanyuan Zhao ; Jingwen Zhou ; Yuanhai Li ; Xiaoqiong Xia
Acta Universitatis Medicinalis Anhui 2023;58(10):1719-1723,1730
Objective :
To study the protective effect and mechanism of remimazolam on cognitive function in septic mice.
Results :
In the LPS group,the number of platform crossing times,the percentage of staying time in the first quadrant,GSH level and SOD activity significantly decreased,and TNF-α, IL-1 β and MDA levels significantly increased.In addition,the arrangement of neurons in CA1 area of hippocampus was disturbed ; cytoplasmic staining was deepened ; and the nucleus was solidly stained.Comparing RM10 ,RM15 and RM20 groups with the LPS group,the number of platform crossing times,the sta- ying time in the first quadrant,GSH level and SOD activity increased,and the levels of TNF-α, IL-1 β and MDA decreased.And the results of hippocampal staining showed a decrease in degenerated neuronal cells.When it came to the comparision in the groups with different doses of remimazolam injection,septic mice in the RM20 group showed less improvement in cognitive dysfunction and inflammatory oxidative stress than the RM10 and RM15 groups.
Conclusion
Remimazolam has a protective effect on cognitive dysfunction in septic mice,and its mechanism may be related to its binding of translocator protein ( TSPO) to inhibit macrophage polarization and thus reduce neuroinflammation and oxidative stress damage.It also reflects that dose of 10 mg / kg and 15 mg / kg has more significant protective effect than that of 20 mg / kg.
5.Protective effect of dexmedetomidine on iron overload⁃induced injury of mouse hippocampal neurons
Hui Ding ; Jingyan Wang ; Yan Huang ; Weiwei Zhong ; Xianfu Lu ; Yuanhai Li
Acta Universitatis Medicinalis Anhui 2022;57(10):1633-1639
Objective :
To investigate the protective effect and related mechanisms of dexmedetomidine (Dex) on iron overload toxicity in mouse hippocampal neurons (HT22) induced by ferric ammonium citrate (FAC) .
Methods:
Selected HT22 cells in good condition were randomly divided into 4 groups: control group ( Ctrl group), FAC treatment group (FAC group), Dex treatment group (Dex group), ferroptosis inhibitor Fer⁃1 treatment group (Fer1 group) . The iron overload model was established by FAC⁃induced cells . Subsequently, the proliferation and survival rate of HT22 cells was detected by CCK⁃8 method; Western blot was used to detect the ferroptosis marker proteins prostaglandin⁃endoperoxide synthase 2 ( PTGS2 ) and acyl⁃CoA synthetase long⁃chain family member 4 (ACSL4) . The protein expressions of mammalian target of rapamycin ( mTOR), transferrin receptor 1 ( TFR1) and ferroportin (Fpn); the gene expression levels of PTGS2 and ACSL4 in HT22 cells were detected by qPCR; Reactive oxygen species (ROS) levels in HT22 cells was detected by DHE fluorescent probe; MDA detection kit was used to detect lipid oxidation levels in HT22 cells; Mito⁃FerroOrange—ferrous ion probe was used to detect ferrous ion levels in HT22 cells; electron microscopy was used to detect intracellular ultrastructural changes .
Results:
Dex group and Fer⁃1 group significantly decreased cell death rate after 2 h of pretreatment, the protein and gene expression levels of ferroptosis markers PTGS2 and ACSL4 significantly decreased . The degree of cell ultrastructural damage was significantly improved . The levels of ROS, lipid oxidation and Fe2 + were significantly lower than those of the FAC group (P < 0. 05) .
Conclusion
Dex pretreatment can attenuate FAC⁃induced iron overload toxicity in⁃ jury in HT22 cells, which may be related to the inhibition of ferroptosis .
6.Effect of dexmedetomidine on intracranial pressure in pediatric patients undergoing laparoscopic surgery: ultrasonographic measurement of optic nerve sheath diameter
Yin XIA ; Yuanhai LI ; Hongwu YE ; Yingying SUN ; Junxia LIU
Chinese Journal of Anesthesiology 2021;41(9):1083-1086
Objective:To evaluate the effect of dexmedetomidine on intracranial pressure in pediatric patients undergoing laparoscopic surgery through measurement of optic nerve sheath diameter (ONSD) by ultrasound.Methods:Ninety-three pediatric patients of both sexes, aged 3-12 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with body mass index of 15.2-18.1 kg/m 2, scheduled for elective laparoscopic appendectomy, were divided into 2 groups using a random number table method: control group (group C, n=45) and dexmedetomidine group (group D, n=48). Dexmedetomidine was infused intravenously in a loading dose of 0.5 μg/kg over 10 min before induction of anesthesia followed by an infusion of 0.5 μg·kg -1·h -1 in group D, while the equal volume of normal saline was given instead in group C. ONSD was measured using ultrasound after entering the operating room (T 0), after tracheal intubation (T 1), at 5 min after pneumoperitoneum (T 2), at 5 min after trendelenburg position (T 3), at the end of anesthesia (T 4) and when orientation recovered (T 5). The development of increased intracranial pressure in pediatric patients was diagnosed according to ONSD.The time for extubation, time for recovery of orientation, the Ramsay score when orientation recovered and postoperative nausea and vomiting were recorded. Results:Compared with group C, ONSD was significantly decreased at T 2, 3, the incidence of increased intracranial pressure was decreased, and the Ramsay score when the patients recovered orientation was increased ( P<0.01), and no significant change was found in the time for extubation, time for recovery of orientation and postoperative nausea and vomiting in group D ( P>0.05). Conclusion:Dexmedetomidine can decrease the development of increased intracranial pressure and produces no effect on the postoperative recovery in pediatric patients undergoing laparoscopic surgery.
7.Clinical Observation of the Application of Etomidate Combined with Propofol in Diagnosis and Treatment of Elderly Patients with Painless Tracheoscope
China Pharmacy 2020;31(24):3031-3035
OBJECTIVE:To o bserve the e fficacy and safety of the application of etomidate combined with propofol in diagnosis and treatment of elderly patients with painless tracheoscope. METHODS :A total of 124 elderly patients with first selective bronchoscopy under general anesthesia were collected from Anhui Chest Hospital during Oct. 2019-May 2020,and then divided into propofol group (group P ),etomidate and propofol group (group EP )according to random number table ,with 62 cases in each group. At anesthesia induction ,Sufentanil citrate injection 5 µg was slowly injected into both groups. Based on this base,group P was given Propofol injectable emulsion 2 mg/kg intravenously ;after the eyelash reflex disappeared ,group P was given intravenous infusion of Propofol injectable emulsion 4 mg/(kg·h)to maintain sedation and Remifentanil hydrochloride for injection 0.1-0.2 µg/(kg·min)to maintain analgesia. Group EP was given slow intravenous injection of 0.5% Propofol injectable emulsion 1 mg/kg+0.1% Etomidate injectable emulsion 0.2 mg/kg;after the eyelash reflex disappeared ,group EP was given intravenous pump of 0.5% Propofol injectable emulsion+ 0.1% Etomidate injectable emulision mixture(1 ∶ 1,V/V)20 mL/h to maintain sedation and Remifentanil hydrochloride for injection to maintain analgesia (same usage and dosage as group P );at the same time ,2 groups were given intravenous injection of Cisatracurium besilate for injection 0.1 mg/kg,the laryngeal mask was inserted into the anesthesia machine for mechanical ventilation ,and then the laryngeal mask w as placed into the tracheoscope fordiagnosis and treatment. Heart rate (HR) and mean arterial pressure (MAP) were observed in 2 groups at the time of entering the room (T1), at the time of eyelash reflex disappearing after anesthesia induction (T2),at the beginning of t racheal intubation examination (T3),10 min after the beginning of the exam ination(T4),at the time of anesthesia recovery (T5),and at the time of leaving the room (T6);operation time,anesthesia recovery time ,the use of vasoactive drugs ,postoperative 4 h cognitive function and adverse reactions were also observed in 2 groups. RESULTS :Two patients in each group were excluded. At T 1,there was no statistical significance in MAP and HR between 2 groups(P>0.05). There was no statistical significance in MAP of group EP among different time points (P> 0.05). MAP and HR of group P at T 2,MAP of group P at T 4,HR of group EP at T 2 were significantly lower than same group at T1,and MAP of group P at T 2 and T 4 were significantly shorter or lower than those of group EP at the same time (P<0.05). The anesthesia recovery time ,the incidence of hypotension and the utilization rate of vasoactive drugs in group EP were significantly lower than group P ;memory ability ,calculation ability and orientation force pass rate of group EP were significantly higher than those of group P of 4 h after operation (P<0.05). There was no statistical significance in operation time ,the incidence of injection pain,muscle spasm ,nausea and vomiting ,focus ability ,language ability ,structure ability ,reasoning ability pass rate between 2 groups(P>0.05). CONCLUSIONS :Etomidate combined with propofol shows good therapeutic efficacy and safety for elderly patients with painless tracheoscope.
8.Effect of different pressure CO2pneumoperitoneum on postoperative gastroeuteric function in female pa-tients undergoing gynecological laparoscopic surgery
Yufei LI ; Shengbin WANG ; Xia JU ; Shenghong HU ; Siqi XU ; Yuanhai LI
The Journal of Clinical Anesthesiology 2018;34(4):359-362
Objective To investigate the effect of different pressure CO2pneumoperitoneum on postoperative gastroeuteric function in female patients undergoing gynecological laparoscopic surgery. Methods A total of 120 female patients,aged 30-60 years,ASA physical status Ⅰ or Ⅱ,scheduled for elective gynecological laparoscopic surgery were randomly into three groups (n=40 in each).The pressure of CO2pneumoperitoneum were set at 6-8,9-11 and 12-14 mm Hg in group L,group M and group H,respectively.All patients were detected on an empty stomach of serum concentrations of D-lactic acid 6 hours before operation and after opration.In addition,pH,PaCO2and PaO2were recor-ded before anesthesia (T1),before pneumoperitoneum (T2),1 hour after pneumoperitoneum (T3)2 hours after pneumoperitoneum (T4)and 1 hour (T5)after stopping pneumoperitoneum.The time of pneumoperitoneum,the time of first flatus,intake and defecation,length of primary hospital stays after operation were recorded.Results Compared with 6 hours before operation,the serum concen-trations of D-lactic acid were obviously increased at postoperative 6 hours in all groups (P<0.05). Compared with group L,the serum concentrations of D-lactic acid at 6 hours after operation were ob-viously increased in group M and group H (P<0.05).PaO2in three groups was not different at T1-T5.Compared with group L,pH at T3,T4was significantly decreased in group M and group H (P<0.05).Compared with group L,PaCO2was significantly increased at T3-T5in group M and group H (P<0.05 ).Compared with group L,the time of first flatus,intake and defecation,length of primary hospital stays after operation were obviously delayed in group M and group H(P<0.05). Conclusion The low pressure of CO2pneumoperitoneum can reduce the damage of CO2pneumoper-itoneum on postoperative gastroeuteric function and avail the recovery of parents’postoperative gas-troeutericfunction in female patients undergoing gynecological laparoscopic surgery.
9.The level of autophagy induced by oxygen glucose deprivation/reperfusion injury in L02 cell
Acta Universitatis Medicinalis Anhui 2017;52(4):475-479
Objective To explore the level of autophagy induced by oxygen glucose deprivation/reperfusion(OGD/R) injury in L02 cell.Methods L02 cells were cultured to establish the model of OGD/R injury and simulate clinical hepatic ischemia-reperfusion injury.The L02 cells were randomly divided into 5 groups : normal control group, oxygen-glucose deprivation 6 h/reperfusion 1,3,6,12 h group (OGD 6 h/R 1,3,6,12 h).Then observe the form changes of the L02 cells by optical microscope.The appreciation of the company's relative L02 cells was detected by MTT.The expression of autophagy related proteins such as Beclin-1, LC3 and p62 were evaluated by Western blot.Results Compared with the normal control group, the form damaged and the cells proliferation activity of L02 cells in the OGD/R group were gradually increased in a time-dependent manner.Compared with the normal control group, autophagy related proteins LC3 , Beclin-1 were increased at OGD 6 h/R 1 h.The expression of LC3 was gradually increased as the time went on and was increased gradually at OGD 6 h/R 6 h, reached a peak at OGD 6 h/R 12 h(P<0.01).The expression of Beclin-1 was gradually increased as the time went on and was increased gradually at OGD 6 h/R 6 h and OGD 6 h/R 12 h (P<0.01).The expression of p62 had no obvious change at OGD 6 h/R 1 h and OGD 6 h/R 3 h, began to increase sharply at OGD 6 h/R 6 h and reached a peak at OGD 6 h/R 12 h(P<0.01).Conclusion Our data suggests that oxygen-glucose deprivation/reperfusion may increase the level of autophagy and lead to autophagic cell death in L02 cell.
10.Effect of different pressure CO2 pneumoperitoneum on early postoperative cognitive function in female ;patients undergoing gynecological laparoscopic surgery
Mengying HU ; Shengbin WANG ; Xia JU ; Shenghong HU ; Siqi XU ; Yuanhai LI
The Journal of Clinical Anesthesiology 2017;33(2):144-147
Objective To investigate the effect of different pressure CO 2 pneumoperitoneum on early postoperative cognitive function in female patients undergoing gynecological laparoscopic sur-gery.Methods Ninety female patients,aged 40-60 years,ASA physical status Ⅰor Ⅱ,scheduled for elective gynecological laparoscopic surgery,were randomly divided into three groups (n = 30). The pressure of CO 2 pneumoperitoneum were set at 6-8,9-1 1 and 12-14 mm Hg in groups L,M and H,respectively.All of the patients were tested by the neuropsychology and questionnaire review to estimate whether the patient got cognitive decline at 24 h before the operation.The venous blood sam-ples 10 minutes before anesthesia (T1 ),at the end of surgery (T2 ),6 hours after surgery (T3 ),24 hours after surgery (T4 )and 72 hours after surgery (T5 )were collected for determination of serum concentrations of NSE and S100βprotein.The pH,PaCO 2 and PaO 2 were recorded before anesthesia (Ta ),before pneumoperitoneum (Tb ),1 hour after pneumoperitoneum (Tc ),2 hours after pneumo-peritoneum (Td )and 1 hour after stopping pneumoperitoneum (Te ).Results Scores of these tests in three groups were not different and there was no patient with cognitive decline after surgery.Com-pared with group H,the concentration of NSE at T2 and T3 was significantly lower in groups L and M (P <0.05).Compared with group H,the concentration of S100βprotein at T2 was significantly lower in groups L and M (P <0.05).Compared with group L,pH at Tc and Td was significantly decreased in groups M and H (P <0.05).Compared with group L,PaCO 2 was significantly increased at Tc-Te in groups M and H (P <0.05).Conclusion Different pressure of CO 2 pneumoperitoneum has no ob-vious effect on the early cognitive function,but low (6-8 mm Hg)CO 2 pneumoperitoneum can reduce the release of NSE and S100βprotein after operation.


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