1.Comparison of the efficacy of remimazolam and propofol in the induction and maintenance of general anesthesia in elderly patients undergoing thoracoscopic lobectomy
Chun LIU ; Juan HU ; Yu HUANG ; Jinqiu YANG ; Junjie LI ; Ping YANG ; Pengfei PAN
China Pharmacy 2025;36(16):2040-2045
		                        		
		                        			
		                        			OBJECTIVE To compare the clinical efficacy and safety of remimazolam and propofol in general anesthesia induction and maintenance for elderly patients undergoing thoracoscopic lobectomy. METHODS A total of 86 elderly lung cancer patients who underwent thoracoscopic lobectomy at Chongqing University Three Gorges Hospital from February to July 2024 were selected and divided into the propofol group and the remimazolam group according to the randomized numerical table method, with 43 cases in each group. During anesthesia induction, patients in the propofol group and the remimazolam group were intravenously administered 2 mg/kg of Propofol medium- and long-chain fat emulsion injection or 0.25 mg/kg of Remimazolam tosilate for injection, respectively; during anesthesia maintenance, the two groups received intravenous infusion of 6-10 mg/(kg·h) of Propofol medium- and long- chain fat emulsion injection or 1-3 mg/(kg·h) of Remimazolam tosilate for injection, respectively. The anesthesia effects, anesthesia-related indicators, intraoperative opioid and muscle relaxant dosages, Ramsay sedation score, numerical rating scale (NRS) score, and hemodynamic parameters were compared between the two groups, and the occurrence of adverse drug reactions was recorded. RESULTS A total of 41 patients in the propofol group and 43 patients in the remimazolam group completed the trial. The proportion of patients with grade Ⅰ anesthesia effect in the remimazolam group was significantly higher than that in the propofol group, while the proportion of patients with grade Ⅱ anesthesia effect was significantly lower than that in the propofol group (P<0.05). In this group, the disappearance time of eyelash reflex, the time taken for the bispectral index to drop to 60, and the Ramsay sedation scores (2 and 6 hours after operation) were all significantly prolonged or increased, while the recovery time, NRS scores (2 and 6 hours after operation), and the incidence of intraoperative hypotension were all significantly shortened or reduced; moreover, the improvements of the above sedation/NRS scores exhibited a time-dependent pattern within 2 to 24 hours after operation (P<0.05). Compared with before anesthesia induction (T0), the heart rate [except at 2 min after medication (T1), 60 min after anesthesia (T4), and at the end of surgery (T5) in the remimazolam group] and mean arterial pressure [except at T1 in the remimazolam group] of patients in both groups significantly decreased at T1, 5 min after medication (T2), at the start of surgery (T3), T4, and T5 (P<0.05). Meanwhile, regional cerebral oxygen saturation significantly increased in both groups. Furthermore, the heart rate and mean arterial pressure of patients in the remimazolam group were significantly higher than those in the propofol group at T1, T2 and T4 (P<0.05). No statistically significant differences were observed between the two groups in terms of postanesthesia care unit stay time, dosage of opioids and muscle relaxants, regional cerebral oxygen saturation, or peripheral oxygen saturation at various time points (P>0.05). CONCLUSIONS Compared to propofol, remimazolam demonstrates superior anesthesia effects when used for the induction and maintenance of general anesthesia in elderly patients undergoing thoracoscopic lobectomy. It not only provides more stable intraoperative hemodynamics and shortens the postoperative recovery time but also effectively reduces the incidence of intraoperative hypotension.
		                        		
		                        		
		                        		
		                        	
2. Effects of Tao Hong Si Wu decoction on IncRNA expression in rats with occlusion of middle cerebral artery
Li-Juan ZHANG ; Chang-Yi FEI ; Chao YU ; Su-Jun XUE ; Yu-Meng LI ; Jing-Jing LI ; Ling-Yu PAN ; Xian-Chun DUAN ; Li-Juan ZHANG ; Chang-Yi FEI ; Chao YU ; Su-Jun XUE ; Yu-Meng LI ; Jing-Jing LI ; Xian-Chun DUAN ; Dai-Yin PENG ; Xian-Chun DUAN ; Dai-Yin PENG
Chinese Pharmacological Bulletin 2024;40(3):582-591
		                        		
		                        			
		                        			 Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD. 
		                        		
		                        		
		                        		
		                        	
3.Drug resistance and genetic diversity of clinical strains of Helicobacter pylori in the Qiannan Prefecture and Guiyang City,and their relationships with diseases
Yuan-Yuan ZHANG ; Ke PAN ; Meng-Heng MI ; Yu-Zhu GUAN ; Qiu-Dan LU ; Juan ZHENG ; Jin ZHANG ; Tian-Shu WANG ; Qi LIU ; Zheng-Hong CHEN
Chinese Journal of Zoonoses 2024;40(1):46-55
		                        		
		                        			
		                        			To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6%(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4%in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.
		                        		
		                        		
		                        		
		                        	
4.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
		                        		
		                        			
		                        			Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
		                        		
		                        		
		                        		
		                        	
5.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
		                        		
		                        			
		                        			Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
		                        		
		                        		
		                        		
		                        	
6.Exploring Symptom Cluster Patterns in Adult Cancer Patients Undergoing Chemotherapy: A Systematic Review
Pan YANG ; Hui-juan MEI ; Hao-yu ZHAO ; Rong-rong WU ; Yong-qin GE ; Yin LU
Journal of Korean Academy of Nursing 2024;54(4):478-494
		                        		
		                        			 Purpose:
		                        			This systematic review aimed to scrutinize the progression of symptom cluster research in adult cancer patients who received primary or adjuvant chemotherapy between 2001 and 2023, providing a comprehensive understanding of clinical practice and future research.  
		                        		
		                        			Methods:
		                        			PubMed, Ovid MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Web of Science databases were searched for theme words and free words related to symptom clusters, cancer, and chemotherapy. Eligible studies were published between January 1, 2001, and May 30, 2023; adults who were diagnosed with cancer and received primary or adjuvant chemotherapy were evaluated.  
		                        		
		                        			Results:
		                        			Twenty-eight studies were included in this review. The Memorial Symptom Assessment Scale emerged as the predominant instrument and exploratory factor analysis was the most frequently employed statistical method to identify symptom clusters. Psychological, gastrointestinal, and physical image symptom clusters were the most commonly delineated. Furthermore, the temporal stability of the symptom clusters showed varying dynamics, with psychological symptom clusters displaying relative consistency over time.  
		                        		
		                        			Conclusion
		                        			Interventions are needed for the most common and stable symptoms in patients with cancer undergoing chemotherapy. Future endeavors may necessitate more longitudinal studies to delve deeper into the temporal stability and dynamic variations of symptom clusters. Such investigations hold promise for advancing symptom cluster research, elucidating the underlying mechanisms, and fostering the development of targeted interventions, thereby enriching the symptom management paradigm in oncological care. 
		                        		
		                        		
		                        		
		                        	
7.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
		                        		
		                        			
		                        			Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
		                        		
		                        		
		                        		
		                        	
8.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
		                        		
		                        			
		                        			Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
		                        		
		                        		
		                        		
		                        	
9.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
		                        		
		                        			
		                        			Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
		                        		
		                        		
		                        		
		                        	
10.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
		                        		
		                        			
		                        			Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
		                        		
		                        		
		                        		
		                        	
            
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