线粒体细胞色素c释放抑制剂对大鼠全脑缺血再灌注损伤炎症反应的作用  

Effect of mitochondrial cytochrome c release inhibitor on the inflammatory response of rats with global cerebral ischemia reperfusion injury

作　　者：方典 梁欢 王佳慧 汪敬业[3] 李正红[1,2] 高琴[1,2] FANG Dian;LIANG Huan;WANG Jia-hui;WANG Jing-ye;LI Zheng-hong;GAO Qin(Department of Physiology,Bengbu Medical College,Bengbu Anhui 233030;Key Laboratory of Cardiovascular and Cerebrovascular Diseases,Bengbu Medical College,Bengbu Anhui 233030;Department of Neurology,The First Affiliated Hospital of Anhui Medical University,Hefei Anhui 230000,China)

机构地区：[1]蚌埠医学院生理学教研室,安徽蚌埠233030 [2]蚌埠医学院心脑血管疾病基础与临床重点实验室,安徽蚌埠233030 [3]安徽医科大学第一附属医院神经内科,安徽合肥230000

出　　处：《蚌埠医学院学报》2022年第1期7-12,共6页Journal of Bengbu Medical College

基　　金：国家自然科学基金项目(81870918);蚌埠医学院心血管基础与临床创新团队(BYKC201906);蚌埠医学院研究生创新计划(Byycxz1912)。

摘　　要：目的:探讨线粒体细胞色素c抑制剂对大鼠全脑缺血再灌注后脑损伤的作用,分析线粒体乙醛脱氢酶2(ALDH2)和炎症反应在其中的机制。方法:通过四血管阻断法模拟大鼠全脑缺血再灌注损伤(I/R)模型,雄性SD大鼠随机分为假手术组(Sham组)、I/R组、ALDH2激动剂Alda-1+I/R组、Bax介导的线粒体细胞色素c释放抑制剂(Bcb)+I/R组。HE染色观察海马CA1区细胞形态学的变化;免疫组织化学观察海马CA1区ALDH2及炎症小体关键蛋白NLRP3表达水平,Western blotting检测海马CA1区4-HNE、NLRP3、IL-1β、IL-18及ALDH2的蛋白水平变化。结果:与Sham组比较,I/R组再灌注7 d后,I/R组海马CA1区细胞存活率明显下降;与I/R组比较,Alda-1+I/R组、Bcb+I/R组的海马CA1区神经元存活率增高(P<0.01)。与I/R组相比,Bcb+I/R组、Alda-1+I/R组海马CA1区ALDH2蛋白表达增加,海马CA1区NLRP3、IL-1β、IL-18、4-HNE蛋白表达下降(P<0.01)。结论:大鼠全脑缺血再灌注损伤模型中,海马CA1区NLRP3表达增高;Bcb可以通过促进线粒体ALDH2的表达、降低炎症反应发挥保护作用。Objective:To explore the effects of mitochondrial cytochrome c inhibitor on the cerebral injury in rats with global cerebral ischemia-reperfusion injury,and analyze the possible mechanisms of mitochondrial aldehyde dehydrogenase 2(ALDH2)and inflammatory response.Methods:The rat model with global cerebral ischemia and reperfusion injury(I/R)was simulated by four-vessel occlusion.The male SD rats were randomly divided into the sham group,I/R group and ALDH2 agonist Alda-1+I/R group and Bax-mediated mitochondrial cytochrome c release inhibitor(Bcb)+I/R group.The HE staining was used to observe the morphological changes of hippocampal CA1 cells.The expressions of ALDH2 protein and inflammasome-related protein NLRP3 in hippocampal CA1 were observed by immunohistochemistry.The protein changes of 4-HNE,NLRP3,IL-1β,IL-18 and ALDH2 in hippocampal CA1 were detected by Western blotting.Results:Compared with the sham group,the survival rate of hippocampal CA1 region cells in the I/R group decreased significantly after 7 d of reperfusion(P<0.01).Compared with the I/R group,the survival rate of hippocampal CA1 neurons in ALDA-1+I/R group and Bcb+I/R group increased(P<0.01).Compared with the I/R group,the expression of ALDH2 protein increased in Bcb+I/R group and ALDA-1+I/R group,while the expressions of NLRP3,IL-1β,IL-18 and 4-HNE proteins in hippocampal CA1 region decreased(P<0.01).Conclusions:The expression of NLRP3 in hippocampal CA1 increases in rats with global cerebral I/R injury model.The Bcb may play a protective role by promoting the mitochondrial ALDH2 expression and reducing inflammatory response.

关 键 词：脑缺血再灌注损伤 线粒体细胞色素c抑制剂 核苷酸结合寡聚化结构域受体蛋白3 线粒体乙醛脱氢酶2 大鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]