海马UQCRC1在小鼠全脑缺血后认知功能障碍中的作用  

Role of hippocampal UQCRC1 in cognitive dysfunction after global cerebral ischemia in mice

作　　者：李加欣 白福海 龙宗泓 张敏 裴洁 刘燕 陈敏琳 张钐钐 李洪 Li Jiaxin;Bai Fuhai;Long Zonghong;Zhang Min;Pei Jie;Liu Yan;Chen Minlin;Zhang Shanshan;Li Hong(Department of Anesthesiology,Second Affiliated Hospital,Army Medical University,Chongqing 400038,China)

机构地区：[1]陆军军医大学第二附属医院麻醉科,重庆400038

出　　处：《中华麻醉学杂志》2024年第12期1499-1504,共6页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(82101273,82171265);陆军军医大学第二附属医院青年博士人才孵化计划(2023YQB007)。

摘　　要：目的评价海马泛醇-细胞色素C还原酶核心蛋白1(UQCRC1)在小鼠全脑缺血(GCI)后认知功能障碍中的作用。方法SPF级健康雄性C57BL/6J小鼠40只,12周龄,体质量22~26 g,其中20只小鼠采用随机数字表法分为2组(n=10):假手术组(Sham组)和GCI1组;另外20只小鼠采用随机数字表法分为2组(n=10):GCI2组和GCI+UQCRC1过表达组(GCI+UQCRC1组)。Sham组仅暴露双侧颈总动脉后直接缝合皮肤;GCI1组、GCI2组和GCI+UQCRC1组采用双侧颈总动脉闭塞法(20 min)制备GCI模型,GCI+UQCRC1组于造模前2周时双侧海马分别注射慢病毒VSVG-Lentivirus-hSyn-EGFP-P2A-UQCRC1-WPRE-pA 500 nl。造模完成后第2天进行新物体识别实验,计算新物体探索时间百分比;造模完成后第3~4天进行恐惧箱实验,记录僵直时间;造模完成后第5~10天行Morris水迷宫实验,记录逃逸潜伏期和目标象限停留时间。水迷宫实验结束后,分别采用免疫荧光法和Western blot法检测海马CA1区UQCRC1表达情况。结果与Sham组比较,GCI1组新物体探索时间百分比降低,训练阶段和测试阶段僵直时间百分比降低,第6~9天逃逸潜伏期延长,目标象限停留时间百分比降低,海马CA1区UQCRC1表达下调(P<0.05);与GCI2组比较,GCI+UQCRC1组新物体探索时间百分比升高,训练阶段和测试阶段僵直时间百分比升高,第6~9天逃逸潜伏期缩短,目标象限停留时间百分比升高,海马CA1区UQCRC1表达上调(P<0.05)。结论海马UQCRC1参与了小鼠GCI后认知功能障碍的过程。Objective To evalaute the role of hippocampal ubiquinol cytochrome C reductase core protein 1(UQCRC1)in cognitive dysfunction after global cerebral ischemia(GCI)in mice.MethodsForty SPF healthy male C57BL/6J mice,aged 12 weeks,weighing 22-26 g,were selected,and 20 of them were divided into 2 groups(n=10 each)using a random number table method:sham operation group and GCI1 group.The other 20 mice were divided into 2 groups(n=10 each)by the random number table method:GCI2 group and GCI+UQCRC1 overexpression group(GCI+UQCRC1 group).In Sham group,the skin was directly sutured after exposing both common carotid arteries.Global cerebral ischemia was induced by occlusion of bilateral common carotid arteries for 20 min in GCI1,GCI2 and GCI+UQCRC1 group,and lentivirus VSVG-Lentivirus-hSyn-EGFP-P2A-UQCRC1-WPRE-pA 500 nl was injected into the bilateral hippocampus at 2 weeks before developing the model in GCI+UQCRC1 group.The novel object recognition task was carried out on the 2nd day following completion of model development,and the percentage of time spent exploring the novel object was calculated.The fear conditioning test was carried out on days 3-4 after completion of model development,and the freezing time was recorded.Morris water maze test was performed on days 5-10 after completion of model development,and the escape latency and time spent in the target quadrant were recorded.After the Morris water maze test,the expression of UQCRC1 in the hippocampal CA1 region was detected by immunofluorescence and Western blot.ResultsCompared with Sham group,the percentage of time spent exploring the novel object was significantly decreased,the percentage of freezing time in training and test stages was decreased,the escape latency on days 6-9 was prolonged,the percentage of time spent in the target quadrant was decreased,and the expression of UQCRC1 in the hippocampal CA1 was down-regulated in GCI1 group(P<0.05).Compared with GCI2 group,the percentage of time spent exploring the novel object was significantly increased,the per

关 键 词：电子传递复合物Ⅲ 脑缺血 认知功能障碍 

分 类 号：R28[医药卫生—中药学]