脑组织IL-6在小鼠心肌梗死后认知障碍中的作用  

Role of interleukin-6 in brain tissues in cognitive impairment after myocardial infarction in mice

作　　者：田瑶 吴超[1] 张野[1] 黄春霞[1] Tian Yao;Wu Chao;Zhang Ye;Huang Chunxia(Department of Anesthesia and Perioperative Medicine,The Second Affiliated Hospital of Anhui Medical University,Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes,Anhui Medical University,Hefei 230601,China)

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

出　　处：《中华麻醉学杂志》2023年第8期991-995,共5页Chinese Journal of Anesthesiology

基　　金：安徽医科大学第二附属医院国家自然科学基金孵育计划(2022GMFY01);安徽省自然科学基金面上项目(2308085MH260)。

摘　　要：目的:评价脑组织IL-6在小鼠心肌梗死后认知障碍中的作用。方法:选取SPF级健康雄性C57/BL6J小鼠40只,SPF级健康雄性IL-6Rα^(flox/flox):CAMKⅡ^(Cre)(IL-6Rα^(NKO))小鼠40只,9月龄,体质量34~39 g,采用随机数字表法,将上述小鼠分别分为2组(n=20):假手术组(Sham组、IL-6Rα^(NKO)-Sham组)和心肌梗死组(MI组、IL-6Rα^(NKO)-MI组)。采用结扎冠状动脉左前降支制备心肌梗死模型。心肌梗死模型制备后28 d,采用心脏超声评估心脏功能,采用巴恩斯迷宫评估认知功能。随后处死小鼠,取脑组织,采用免疫荧光染色法检测海马CA3区IL-6、c-Fos、小胶质细胞活化标志物离子钙结合衔接分子(Iba1)、星形胶质细胞活化标志物胶质纤维酸性蛋白(GFAP)的表达水平。透射电镜观察突触结构,计数突触数量,测定突触后致密区(PSD)厚度。结果:与各假手术组相比,心肌梗死组射血分数和短轴缩短率降低,左室收缩末期内径升高(P<0.05)。与Sham组相比,MI组巴恩斯迷宫潜伏期延长,海马CA3区IL-6、c-Fos、GFAP和Iba1表达上调,突触数量和PSD厚度减少(P<0.05)。与IL-6Rα^(NKO)-Sham组相比,IL-6Rα^(NKO)-MI组海马神经元突触数量减少(P<0.05),其余指标差异无统计学意义(P>0.05)。与MI组相比,IL-6Rα^(NKO)-MI组巴恩斯迷宫潜伏期缩短,海马CA3区IL-6、c-Fos、GFAP和Iba1表达下调,突触数量和PSD厚度增加(P<0.05)。结论:小鼠心肌梗死后认知障碍的机制可能与IL-6介导中枢神经炎症反应,引起海马突触损伤有关。Objective To evaluate the role of interleukin-6(IL-6)in brain tissues in cognitive impairment after myocardial infarction in mice.Methods Forty SPF healthy male C57/BL6J mice and 40 IL-6Rα^(flox/flox):CAMKⅡ^(Cre)(IL-6Rα^(NKO))mice,aged 9 months,weighing 34-39 g,were divided into 2 groups(n=20 each)using a random number table method:sham operation group(Sham group,IL-6Rα^(NKO)-Sham group)and myocardial infarction group(MI group,IL-6Rα^(NKO)-MI group).Myocardial infarction model was developed by ligating the left anterior descending coronary artery in anesthetized animals.The same surgery was performed without ligation of blood vessels in Sham group.At 28 days after preparing the myocardial infarction model,cardiac function was assessed by cardiac doppler echocardiography,and cognitive function was assessed using the Barnes maze test.Then mice were sacrificed,and brain tissues were collected for determination of the expression of IL-6,c-Fos,ionized calcium-binding adaptor molecule 1(Iba-1,a marker protein for microglia activation)and glial fibrillary acidic protein(GFAP)(by immunofluorescence staining)in the hippocampal CA3 region.The ultrastructure of synapses in the hippocampi was examined with a transmission electron microscope to record the number of synapses and thickness of postsynaptic density(PSD).Results Compared with sham operation groups,the ejection fraction and shortening rate of short axis were significantly decreased,and the left ventricular end-systolic diameter was increased in myocardial infarction groups(P<0.05).Compared with Sham group,the latency to reach the target hole was significantly prolonged in the Barnes maze test,the expression of IL-6,c-Fos,GFAP and Iba1 was up-regulated in the hippocampal CA3 region,and the number of synapses and thickness of PSD were decreased in MI group(P<0.05).Compared with IL-6Rα^(NKO)-Sham group,the number of synapses in hippocampal neurons was significantly decreased(P<0.05),and no significant change was found in the other parameters in IL-6Rα^(NKO)-MI

关 键 词：心肌梗死 认知障碍 白细胞介素6 突触 

分 类 号：R542.22[医药卫生—心血管疾病] R749.1[医药卫生—内科学]