cGAS抑制剂对小鼠脑缺血再灌注损伤的干预作用及其机制  

Intervention effect and mechanism of cGAS inhibitor on cerebral ischemia reperfusion injury in mice

作　　者：黄丽丹 李冰玉 李亚男 王苏[1] 龚平 HUANG Lidan;LI Bingyu;LI Ya'nan;WANG Su;GONG Ping(Department of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,China;不详)

机构地区：[1]武汉大学人民医院麻醉科,武汉430060 [2]武汉大学口腔医院麻醉科、口腔基础医学省部共建国家重点实验室培育基地和口腔生物医学教育部重点实验室

出　　处：《山东医药》2023年第8期21-24,共4页Shandong Medical Journal

基　　金：国家自然科学基金项目(82102295)。

摘　　要：目的观察cGAS抑制剂对小鼠脑缺血再灌注损伤的干预作用,并基于自噬调节探讨相关机制。方法雄性C57BL/6小鼠18只,随机分为假手术组、模型组、实验组,每组6只。模型组、实验组采用线栓法制备大脑中动脉栓塞模型,实验组在再灌注前10 min腹腔注射5 mg/kg的cGAS抑制剂RU.521,假手术组分离大脑中动脉但不阻断。再灌注6 h后行HE染色、Nissl染色观察脑组织病理变化,Western blotting法检测脑组织中的cGAS、LC3B、Beclin-1蛋白,免疫荧光法检测凋亡细胞并计算凋亡率。结果与假手术组相比,模型组神经元数量减少,细胞固缩,实验组上述改变减轻。模型组脑组织中cGAS、LC3B、Beclin-1蛋白相对表达量及细胞凋亡率高于假手术组,实验组cGAS、LC3B、Beclin-1蛋白表达及细胞凋亡率低于模型组(P均<0.05)。结论cGAS抑制剂预处理可减轻小鼠脑缺血再灌注损伤,其机制可能与调节自噬相关蛋白表达有关。Objective To investigate the intervention effect of cGAS inhibitor on cerebral ischemia reperfusion inju⁃ry in mice,and to explore the related mechanism based on autophagy.Methods Eighteen C57BL/6 male mice were ran⁃domly divided into three groups:sham group,model group,and experimental group,with 6 in each.In the model group and experimental group,the middle cerebral artery occlusion model was prepared by suture method.Mice in the experi⁃mental group received intraperitoneal injection of 5 mg/kg cGAS inhibitor RU.521 within 10 min before reperfusion.In the sham group,the middle cerebral artery was isolated but not blocked.After 6 h of reperfusion,the HE staining and Nissl staining was performed.The protein levels of cGAS,LC3B and Beclin-1 were detected by Western blotting.Apopto⁃sis was detected by immunofluorescence.Results Compared with the sham group,the model group showed a reduced number of neurons and cellular consolidation.All the changes were alleviated after the administration of cGAS inhibitor.Compared with the sham group,cGAS,LC3B,Beclin-1 and apoptosis in the model group increased.Compared with the model group,cGAS,LC3B,Beclin-1 and apoptosis in the experimental group decreased(all P<0.05).Conclusion cGAS inhibitor can effectively reduce cerebral ischemia reperfusion injury probably by regulating the expression of autopha⁃gy-related proteins.

关 键 词：环状GMP-AMP合酶抑制剂 细胞自噬 脑缺血再灌注损伤 

分 类 号：R614[医药卫生—麻醉学]