黄体酮对阿尔茨海默病大鼠脑海马水通道蛋白4表达的调控及其在阿尔茨海默病治疗中的作用  

Regulation of progesterone on hippocampus aquaporin 4 expression and its role in the treatment of Alzheimer's disease rats

作　　者：陈小奇 李进 杨洪清 CHEN Xiaoqi;LI Jin;YANG Hongqing(Dept.of Neurology,Affiliated Hospital of Jianghan University&Wuhan Sixth People's Hospital,Wuhan 430015,Hubei,China;Dept.of Neurology,Genral Hospital of The Yangtze River Shipping&Wuhan Brain Hospital,Wuhan 430015,Hubei,China;Dept.of Neurology,Laohekou First People's Hospital,Xiangyang 441899,Hubei,China)

机构地区：[1]江汉大学附属医院/武汉市第六医院神经内科,湖北武汉430015 [2]长江航运总医院/武汉脑科医院神经内科,湖北武汉430015 [3]老河口市第一人民医院神经内科,湖北襄阳441899

出　　处：《武汉大学学报(医学版)》2025年第3期307-313,共7页Medical Journal of Wuhan University

摘　　要：目的:探讨黄体酮(PROG)对阿尔茨海默病(AD)鼠脑海马AQP4表达的调控效应,及其在AD治疗中的作用。方法:应用Aβ25-35联合D-半乳糖的方法诱导AD模型,并使用黄体酮(PROG+AD)进行治疗;使用Morris水迷宫检测各组大鼠的学习记忆能力,应用HE染色法检测各组鼠脑海马的形态结构,应用免疫荧光染色法检测各组鼠脑AQP4的表达定位,使用免疫印迹法检测各组鼠脑AQP4的表达量。结果:水迷宫结果显示,与Sham组比较,AD组的逃避潜伏期和搜索路径均增加(P<0.05),穿越平台次数减少(P<0.05);PROG+AD组可逆转AD组的上述改变(P<0.05);HE染色显示,AD组鼠脑海马锥体层细胞排列紊乱,细胞数量减少,空泡逐渐增多,PROG处理可减轻AD组以上改变;免疫荧光结果显示,Sham组海马位于血管周围,AD组海马AQP4表达增加,主要位于细胞膜上;PROG+AD组AQP4表达减少,在细胞膜及血管周围均有表达。免疫印迹结果显示,AD组海马AQP4表达较Sham组增加(P<0.05),PROG+AD组AQP4表达较AD组下降(P<0.05)。结论:黄体酮可改善AD鼠的学习记忆能力,其机制与下调AD鼠脑AQP4的表达量及恢复其极性表达部位有关。Objective:To study the regulatory effect of progesterone(PROG)on the expression of Aquaporin-4(AQP4)in the hippocampus of the Alzheimer's disease(AD)rat model and to investigate the therapeutic effect and mechanism of PROG on AD.Methods:AD rat models were induced by Aβ25-35 combined with D-galactose and treated with progesterone(PROG+AD);Morris water maze was applied to show the learning and memory capacity of rats in each group;HE staining was used to detect the pathological changes of hippocampus;immunofluorescence staining was used to detect the expression location of hippocampus AQP4;Western Blot was used to detect the expression abundance of hippocampus AQP4.Results:The results of Morris water maze showed that compared with those in Sham group,the escape latency and search path of AD group increased(P<0.05),and the times of crossing the quadrant where the platform was located decreased(P<0.05);PROG could reverse the above changes in AD group(P<0.05).HE staining results showed that the hippocampal pyramidal neurons in AD group were disordered,the number of cells decreased,and vacuoles gradually increased;PROG treatment could alleviate the pathological changes in AD group.Immunofluorescence staining showed that the hippocampus AQP4 of Sham group was located around the blood vessels,while the expression of hippocampus AQP4 in the AD group increased and located mainly on the cell membrane.The expression of AQP4 in the PROG+AD group decreased,and AQP4 was partly located in the cell membrane and around blood vessels.Western Blot results showed that the expression of hippocampus AQP4 in AD group was higher than that of Sham group(P<0.05),while the expression of hippocampus AQP4 in PROG+AD group was lower than that of AD group.Conclusion:Progesterone can improve the learning and memory ability of AD rats,and its mechanism is related to the down-regulation of hippocampus AQP4 expression in the brain of AD rats and the restoration of its polar expression site.

关 键 词：阿尔茨海默病 β-淀粉样蛋白 黄体酮 海马 水通道蛋白4 

分 类 号：R741.03[医药卫生—神经病学与精神病学]