海马区GSDMD-N介导的小胶质细胞焦亡在大鼠心肺复苏脑损伤模型中的研究  

GSDMD-N mediated hippocampal microglial pyroptosis in a rat model of brain injury after cardiopulmonary resuscitation

作　　者：闫玉婷 武丽敏 赵钊艳 马港国 高昌俊 YAN Yuting;WU Limin;ZHAO Zhaoyan;MA Gangguo;GAO Changjun(Department of Anesthesiology,Air Force Medical University,Xi'an 710038,China;Department of Neurosurgery,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China)

机构地区：[1]空军军医大学唐都医院麻醉科,陕西西安710038 [2]空军军医大学唐都医院神经外科,陕西西安710038

出　　处：《空军军医大学学报》2023年第4期305-310,共6页Journal of Air Force Medical University

基　　金：国家自然科学基金(81971225);陕西省自然科学基础研究计划重点项目(2023-JC-ZD-52)。

摘　　要：目的 探索大鼠心肺复苏(CPR)脑损伤后海马区小胶质细胞的激活和焦亡情况。方法 建立CPR脑损伤模型,将30只雄性SD大鼠随机分为假手术组(Sham组)和CPR脑损伤组(CPR组),每组15只。采用旷场试验和Morris水迷宫实验分析大鼠的行为变化,确定CPR后脑损伤对负性情绪和认知功能的影响;通过免疫荧光染色技术、流式细胞术和Western blotting观察海马区小胶质细胞的激活、焦亡及相关蛋白的表达情况。结果与Sham组相比,在旷场和Morris水迷宫实验中,CPR组大鼠出现焦虑、抑郁情绪和认知功能障碍(P<0.05);Western blotting结果显示,CPR组大鼠海马组织中的焦亡相关蛋白表达增多(P<0.05);免疫荧光和流式细胞术结果显示,CPR组大鼠海马区小胶质细胞被大量激活,焦亡效应蛋白GSDMD-N表达上调且与激活的小胶质细胞实现了共定位。结论 CPR脑损伤后,海马区GSDMD-N将介导小胶质细胞的焦亡。Objective To explore the activation and pyroptosis of microglia in the hippocampus after brain injury induced by cardiopulmonary resuscitation(CPR)in rats.Methods A rat model of brain injury after CPR was established.Thirty male SD rats were randomly divided into sham-operated group(Sham group)and CPR-induced brain injury group(CPR group),with 15 rats in each group.The behavioral changes of rats were analyzed by open field test and Morris water maze test to determine the effects of brain injury after CPR on negative emotion and cognitive function.Immunofluorescence staining,flow cytometry and Western blotting were used to observe the activation,pyroptosis and expression of related proteins of microglia in the hippocampus.Results Compared with Sham group,anxiety,depression and cognitive dysfunction were observed in CPR group in open field and Morris water maze tests(P<0.05).Western blotting results showed that the expression of pyroptosis-related proteins increased in the hippocampus of CPR group(P<0.05).Immunofluorescence and flow cytometry results showed that microglia in the hippocampus of CPR group were significantly activated,and the expression of pyroptotic effector protein GSDMD-N was up-regulated and co-localized with activated microglia.Conclusion In hippocampus,GSDMD-N may mediate microglial pyroptosis after brain injury induced by CPR.

关 键 词：心肺复苏 脑损伤 海马 小胶质细胞 GSDMD-N 细胞焦亡 

分 类 号：R459.7[医药卫生—急诊医学]