SIRT1介导的七氟醚后处理对失血性休克复苏小鼠学习与记忆损伤的保护作用  

The protective effects of sevoflurane postconditioning mediated by SIRT1 onlearning and memory impairment in hemorrhagic shock and resuscitation mice

作　　者：黄晓童 黄春霞[1] 胡宪文[1] HUANG Xiao-tong;HUANG Chun-xia;HU Xian-wen(Key Lab of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes,Dept of Anesthesiology and Perioperative Medicine,the Second Hospital of Anhui Medical University,Hefei 230601,China)

机构地区：[1]麻醉与围术期医学安徽普通高校重点实验室,安徽医科大学第二附属医院麻醉与围术期医学科,安徽合肥230601

出　　处：《中国药理学通报》2021年第3期385-390,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81801050);安徽医科大学基础与临床合作研究提升计划(No 2019xkjT026)。

摘　　要：目的探究沉默信息调节因子(silent information regulation 1,SIRT1)介导的凋亡相关通路在七氟醚后处理对失血性休克复苏小鼠海马神经元损伤中的保护作用。方法建立失血性休克与复苏小鼠模型,雄性C57BL/6J小鼠60只随机分为:假手术组(Sham组)、HSR组(Shock组)、七氟醚处理组(Sevo组)、七氟醚联合SIRT1特异性抑制剂处理组(EX527+Sevo组)以及EX527处理组(EX527组)。通过TTC染色法检测小鼠脑梗死体积,TUNEL染色法检测各组小鼠海马神经细胞的变化,水迷宫实验检测小鼠学习记忆能力,Western blot检测SIRT1和凋亡相关蛋白Bcl-2、Bax、Cleaved caspase-3的表达。结果造模小鼠在水迷宫检测中到达平台的潜伏期延长,在目标象限的运动距离减少,脑梗死体积增大,TUNEL染色阳性细胞数增多,SIRT1、Bcl-2蛋白表达降低,Bax、Cleaved-caspase3蛋白表达增加;七氟醚处理后改善了失血性休克与复苏小鼠的神经损伤情况,七氟醚与SIRT1抑制剂EX527联合处理后,七氟醚对失血性休克与复苏小鼠的神经损伤保护作用减弱。结论七氟醚可能通过SIRT1介导的凋亡相关通路发挥对失血性休克复苏引起的海马神经元损伤的保护作用。Aim To explore the role of the silent information regulator(silent information regulation 1,SIRT1)-mediated apoptotic pathway in the protection of sevoflurane postconditioning in hippocampal neuronal injury of mice induced by hemorrhagic shock resuscitation(HSR).Methods A mouse model of HSR was established.The male C57BL/6J mice were randomly divided into:sham operation group(Sham group),HSR group(Shock group),sevoflurane treatment group(Sevo group),sevoflurane combined with SIRT1 specific inhibitor treatment group(EX527+Sevo group)and EX527 treatment group(EX527 group).The volume of cerebral infarction was detected by TTC staining method.The changes of hippocampal nerve cells in each group of mice were detected by TUNEL staining method.The learning and memory abilities were detected by Morris water maze test.The expression of SIRT1 and apoptosis-related protein levels were detected by Western blot analysis.Results The latency of the model mice reaching the platform in Morris water maze test was prolonged,while the movement distance in the target quadrant was similarly reduced.Besides,the cerebral infarction volume remarkably increased.The number of TUNEL staining positive cells increased,and the expression of SIRT1 and Bc1-2 decreased while the pro-apoptosis protein Bax,and cleaved-caspase 3 expression level increased;sevoflurane treatment improved nerve injury in HSR.After combined treatment with sevoflurane and SIRT1 inhibitor EX527,the protective effect of sevoflurane was attenuated on nerve injury in HSR.Conclusion Sevoflurane may play a protective role against hippocampal neuronal injury caused by HSR mediated by SIRT1 apoptosis-related pathway.

关 键 词：七氟醚 失血性休克复苏 SIRT1 水迷宫 凋亡:神经损伤 保护作用 

分 类 号：R-332[医药卫生—人体解剖和组织胚胎学] R322.81[医药卫生—基础医学]