七氟醚预处理对老年大鼠认知功能障碍的影响及海马区自噬在其中的作用研究  

Effects of sevoflurane preconditioning on cognitive dysfunction in aged rats and the role of autophagy in the hippocampus

作　　者：谢翼[1] 王凯[2] 牛敏 XIE Yi;WANG Kai;NIU Min(ZiBo Central Hospital of Shandong Province,Zibo 255034;China.2.Rizhao People’s Hospital of Shandong Province,Rizhao 276800)

机构地区：[1]山东省淄博市中心医院,山东淄博255034 [2]山东省日照市人民医院,山东日照276800

出　　处：《中国比较医学杂志》2020年第11期84-90,共7页Chinese Journal of Comparative Medicine

摘　　要：目的探讨海马区自噬对七氟醚诱导老年大鼠认知功能障碍的影响及可能机制。方法72只SD大鼠随机分为对照组(CON)、自噬诱导剂雷帕霉素组(RAP)、自噬抑制剂氯喹组(CQ)、七氟醚组(SEV)、七氟醚+雷帕霉素组(SEV+RAP)、七氟醚+氯喹组(SEV+CQ),每组12只。各组大鼠进行血气指标检测;Morris水迷宫测试大鼠学习记忆能力;透射电子显微镜观察海马区神经元的超微结构的改变;TUNEL法染色观察海马CA1区神经元凋亡情况;RT-q PCR检测大鼠LC3 mRNA的表达;Western blot检测海马组织中p-S6K1、Cl-Caspase3、p62、p-m TOR、Bax、Bcl-2蛋白表达。结果与对照组比较,各组大鼠血气分析无显著性差异(P>0.05);与CON组比较,SEV组逃避潜伏期延长(P<0.01),目标象限时间百分比缩短(P<0.05),穿越平台次数减少(P<0.01),海马组织中p62、cl-caspase3和Bax蛋白表达升高(P<0.05),Bcl-2蛋白表达降低(P<0.01),海马CA1区中自噬泡数量和细胞凋亡率增加(P<0.01);与SEV组比较,SEV+RAP组目标象限时间百分比延长(P<0.05)、逃避潜伏期缩短(P<0.05),穿越平台次数增加(P<0.05),海马组织中p62、p-m TOR、p-S6K1、Cl-caspase3和Bax蛋白表达降低(P<0.05),海马组织中LC3 mRNA及Bcl-2蛋白表达升高(P<0.01),海马自噬泡数量和细胞凋亡率增加(P<0.01)。结论七氟醚麻醉导致老年大鼠认知功能障碍可能与海马神经元的自噬受损有关。Objective To investigate the effect of hippocampal autophagy on sevoflurane-induced cognitive impairment in aged rats and its possible mechanism.Methods Seventy-two Sprague-Dawley rats were randomly divided into 6 groups:CON,RAP,CQ,SEV,SEV+RAP,and SEV+CQ.The following method were used to collect data from each group:blood gas indexes;learning and memory ability testing by Morris water maze;ultrastructural changes of hippocampal neurons under transmission electron microscopy;apoptosis of hippocampal CA1 neurons observed by terminal deoxynucleotidyl transferase d UTP nick end labeling;quantification of LC3 mRNA expression by reverse transcriptionquantitative PCR;and protein expression of p62,LC3,Caspase3,Bax and Bcl-2 in the hippocampus detected by Western blot.Results There were no significant differences in arterial blood gas result in the 6 groups of rats(P>0.05).Compared with the CON group,in the SEV group the escape latency was prolonged(P<0.01),the percentage of target quadrant time was shortened(P<0.05),and the number of crossing platforms was reduced(P<0.01),while the expression of p62,cleaved caspase-3 and Bax protein increased in the hippocampus(P<0.05),Bcl-2 decreased(P<0.01),and the number of autophagic vesicles and the rate of apoptosis were increased in the hippocampus(P<0.01).Compared with the SEV group,the escape latency of the SEV+RAP group was decreased(P<0.01).Additionally,the expression of p62,p-mTOR,p-s6 k1,cl-caspase-3 and Bax protein were all decreased in the hippocampus(P<0.05),while the expression of LC3 mRNA and bcl-2 protein increased(P<0.01),and the number of autophagic vesicles and the rate of apoptosis increased(P<0.01)in the hippocampus.Conclusions Cognitive dysfunction caused by sevoflurane anesthesia in elderly rats may be related to impaired autophagy in hippocampal neurons.

关 键 词：七氟醚 自噬 认知功能障碍 雷帕霉素 老年大鼠 

分 类 号：R-33[医药卫生]