Homer1a/mGluR5信号通路在睡眠剥夺致老龄大鼠认知功能障碍中的作用  

Role of Homer1a/mGluR5 signaling pathway in cognitive dysfunction induced by sleep deprivation in aged rats

作　　者：李运 杨陈祎 王心怡 冯磊[2] 孙熠[2] 杨卓[3] 王海云[2] Li Yun;Yang Chenyi;Wang Xinyi;Feng Lei;Sun Yi;Yang Zhuo;Wang Haiyun(The Third Center Clinical College of Tianjin Medical University,Tianjin 300170,China;Department of Anesthesiology,Tianjin Third Center Hospital,Nankai University Affinity the Third Central Hospital,The Third Center Clinical College of Tianjin Medical University,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases,Tianjin Artificial Cell Engineering Technology Research Center,Tianjin Hepatobiliary Research Institute,Tianjin 300170,China;College of Medicine,Nankai University,Tianjin 300071,China)

机构地区：[1]天津医科大学三中心临床学院,天津300170 [2]天津市第三中心医院麻醉科、南开大学附属第三中心医院、天津医科大学三中心临床学院、天津市重症疾病体外生命支持重点实验室、天津市人工细胞工程技术研究中心、天津市肝胆研究所,天津300071 [3]南开大学医学院,天津300071

出　　处：《中华麻醉学杂志》2023年第6期697-701,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金面上项目(82071220);天津市自然科学基金面上项目(20JCYBJC01290);天津市医学重点学科(专科)建设项目(TJYXZDXK-072C);天津市应用基础研究多元投入基金项目(21JCQNJC01020)。

摘　　要：目的评价Homer1a/代谢型谷氨酸受体5(mGluR5)信号通路在睡眠剥夺致老龄大鼠认知功能障碍中的作用。方法SPF级健康雄性SD大鼠104只,22~24月龄,体质量320~360 g,采用随机数字表法分为4组(n=26):正常对照组(Control组)、睡眠剥夺+溶剂组(SD+Vehicle组)、睡眠剥夺+mGluR5正向变构剂CDPPB组(SD+CDPPB组)和睡眠剥夺+mGluR5拮抗剂MPEP组(SD+MPEP组)。采用剥夺杆法建立48 h睡眠剥夺模型。SD+CDPPB组、SD+MPEP组和SD+Vehicle组于造模开始和24 h时分别腹腔注射CDPPB 10 mg/kg、MPEP 10 mg/kg和等容量1%Tween 80。造模结束后行Morris水迷宫实验和新物体识别实验评估认知功能,采用Western blot法检测海马Homer1a和mGluR5的表达,高尔基染色法检测海马CA1区树突棘密度,离体电生理技术检测海马CA1区场兴奋性突触后电位(fEPSP)斜率。结果与Control组比较,SD+Vehicle组穿越原平台位置次数、目标象限停留时间和训练后1、24 h时新物体识别指数降低,海马Homer1a表达上调,mGluR5表达下调,CA1区树突棘密度和fEPSP斜率降低(P<0.05);与SD+Vehicle组比较,SD+MPEP组穿越原平台位置次数、目标象限停留时间和训练后1、24 h时新物体识别指数升高,海马mGluR5表达上调,CA1区树突棘密度和fEPSP斜率升高(P<0.05),SD+CDPPB组上述指标差异无统计学意义(P>0.05)。结论睡眠剥夺通过调控Homer1a/mGluR5信号通路,损伤海马神经元突触可塑性,介导老龄大鼠认知功能障碍的过程。Objective To evaluate the role of Homer1a/metabotropic glutamate receptor 5(mGluR5)signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods One hundred and four SPF healthy male Sprague-Dawley rats,aged 22-24 months,weighing 320-360 g,were divided into 4 groups(n=26 each)using a random number table method:normal control group(group Control),sleep deprivation+vehicle group(group SD+Vehicle),sleep deprivation+mGluR5 forward allosteric agent CDPPB group(group SD+CDPPB),and sleep deprivation+mGluR5 antagonist MPEP group(group SD+MPEP).A 48-h sleep deprivation model was developed by sleep-deprived rod method.At the beginning of developing the model and 24 h after developing the model,CDPPB 10 mg/kg,MPEP 10 mg/kg and the equal volume of 1%Tween 80 were intraperitoneally injected in group SD+CDPPB,group SD+MPEP and group SD+Vehicle,respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model.The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot,the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining,and the field excitatory postsynaptic potential(fEPSP)slope in the hippocampal CA1 region was detected by isolated electrophysiology.Results Compared with Control group,the number of crossing the original platform,time of staying at the target quadrant,and novel object recognition index at 1 and 24 h after training were significantly decreased,the expression of Homer1a in the hippocampus was up-regulated,the expression of mGluR5 in the hippocampus was down-regulated,and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+Vehicle(P<0.05).Compared with group SD+Vehicle,the number of crossing the original platform,time of staying at target quadrant,and novel object recognition index at 1 and 24 h after training were significantly increased,the expression of mGluR5 in hippocampus was up-regulated,and t

关 键 词：睡眠剥夺 认知功能障碍 老年人 海马 Homer支架蛋白质类 受体 代谢性谷氨酸5型 

分 类 号：R614[医药卫生—麻醉学]