七氟烷介导BDNF-mTOR信号通路改善低温失血性休克大鼠空间学习记忆能力

BDNF-mTOR signaling mediated by sevoflurane to improve spatial learning and memory in hemorrhagic shock rats

目的探讨七氟烷对大鼠低温失血性休克大鼠空间学习记忆能力的作用及机制。方法24只SPF级雄性SD大鼠,随机分为假手术(Sham)组,低温失血性休克(HS)组和七氟烷处理低温失血性休克(Sev)组,采用Morris水迷宫方法检测大鼠空间学习记忆能力;HE染色观察大鼠脑组织病理变化;免疫荧光方法检测海马组织ROS与BDNF表达水平;Golgi-Cox染色观察大鼠脑组织海马区神经元树突结构和生长情况;Western blot检测大鼠脑组织BDNF-mTOR信号通路相关蛋白表达水平。结果低温失血性休克(HS)组大鼠Morris水迷宫实验出现异常行为;脑组织细胞排列紊乱;脑组织海马区ROS含量升高、神经元树突结构减少、BDNF、p-TrkB和-mTOR蛋白表达水平显著降低;而七氟烷处理复苏低温失血性休克大鼠,大鼠表现及信号表达均得到改善。结论七氟烷可能通过调控BDNF-mTOR信号通路改善低温失血性休克造成的脑损伤,改善大鼠空间学习记忆能力。

Objective To explore the effect and mechanism of sevoflurane on spatial learning and memory ability of rats with hypothermia hemorrhagic shock.Methods 24 SPF male SD rats were randomly divided into sham group,HS group and sevoflurane treated hemorrhagic shock(Sev)group.The spatial learning and memory ability of rats was detected by morris water maze.The pathological changes of brain tissue were observed by HE staining.The expressions of ROS and BDNF in hippocampus were detected by immunofluorescence method.The structure and growth of neuronal dendrites in hippocampus of rats was observed by Golgi-Cox staining.The expressions of BDNF-mTOR signaling pathway related proteins in rat brain were detected by Western blot.Results The rats in hemorrhagic shock(HS)group showed abnormal behavior in morris water maze test,arrangement of brain cells was disordered,content of ROS in hippocampus was increased,neuronal dendrite structure was decreased,and the expressions of BDNF,p-TrkB and-mTOR were decreased significantly.After sevoflurane treatment,the performance and signal expression of rats in hypothermia hemorrhagic shock were improved.Conclusion Sevoflurane may improve the brain injury caused by hypothermia hemorrhagic shock and improve the spatial learning and memory ability of rats by regulating BDNF-mTOR signaling pathway.