七氟醚激活海马线粒体自噬诱导老年小鼠认知功能损伤

目的 探讨七氟醚对老年小鼠海马线粒体自噬和认知功能的影响.方法 雄性C57BL/6J小鼠48只,18～20月龄,体重35～40 g.采用随机数字表法将小鼠为三组:对照组(C组)、吸入3％七氟醚组(S组)和吸入3％七氟醚+自噬抑制剂三甲基腺嘌呤组(3-MA组),每组16只.C组小鼠吸入空氧混合气体6 h.S组和3-MA组...

Sevoflurane activates hippocampal mitophagy and thereby induces cognitive decline in aged mice

Objective To investigate the effects of sevoflurane on hippocampal mitophagy and cognitive function in aged mice.Methods Forty-eight male C57BL/6J mice,aged 18-20 months,weighing 35-40 g,were randomly divided into three groups(n=16 in each group):control group(group C),3%sevoflurane group(group S)and 3%sevoflurane plus 3-MA group(group 3-MA).Mice in group C inhaled air for 6 hours.Mice in group S and group 3-MA inhaled 3%sevoflurane for 6 hours.Mice in group 3-MA received an intraperitoneal injection of 3-methyladenine(30 mg/kg)1 hour before sevoflurane inhalation.The Morris water maze(MWM)test was performed 24 hours after sevoflurane inhalation in all groups.Training was performed on the 1 st to 4 th day and testing was performed on the 5 th day.Mice were sacrificed immediately after the behavior test and the brains were taken out for hematoxylin-eosin staining and immunofluorescence.Hippocampal expressions of PINK1,Parkin,LC3 and Beclin1 were detected by Western blot.Results Compared with group C,the escape latency prolonged significantly on the 2 nd to 4 th day of MWM test,and the residence time and number of crossings in the target quadrant on the 5 th day decreased significantly in groups S and 3-MA(P<0.05);the pathomorphology of the hippocampus was obviously damaged in groups S and 3-MA;the hippocampal number of LC3 positive cells,the ratio of LC3Ⅱ/LC3Ⅰand the expressions of PINK1,Parkin and Beclin1in mice in groups S and 3-MA were higher(P<0.05).Compared with group S,the escape latency shortened significantly on the 2 nd to 4 th day of MWM test,and the residence time and number of crossings in the target quadrant on the 5 th day increased significantly in group 3-MA;the pathomorphological damage of the hippocampus was attenuated in group 3-MA;the hippocampal number of LC3 positive cells,the ratio of LC3Ⅱ/LC3Ⅰand the expressions of PINK1,Parkin and Beclin1 were decreased in group 3-MA(P<0.05).Conclusion Aged mice inhaled 3%sevoflurane for 6 hours display hippocampal morphology damage and decline in the ability of learning and memory.The mechanism may be related to the activation of mitophagy.