胃旁路手术对阿尔茨海默病模型小鼠认知功能的影响  

Effects of gastric bypass surgery on cognitive function in mice with Alzheimer’s disease

作　　者：李禹兵[1] 高凌[1] 罗登[1] 叶迎春[1] 周芬 LI Yubing;GAO Ling;LUO Deng;YE Yingchun;ZHOU Fen(Department of Endocrinology,Remin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院内分泌科

出　　处：《疑难病杂志》2019年第8期831-836,共6页Chinese Journal of Difficult and Complicated Cases

基　　金：国家自然科学基金资助项目(81571376);中华国际医学交流基金会项目(2018HX0003)

摘　　要：目的观察胃旁路手术对APP/PS1/Tau三转基因阿尔茨海默病模型小鼠(AD模型小鼠)认知功能的影响。方法 2018年2月—2019年3月在武汉大学人民医院中心实验室及动物实验中心进行实验,选取来自亲代APP/PS1/Tau三转基因型的子代小鼠(6月龄)随机分为AD胃旁路手术组(n=6)、AD模型组(n=6),另取相同月龄同窝生的C57小鼠随机分为WT正常对照组(n=6)、WT正常胃旁路手术组(n=6)。胃旁路手术2个月后进行APP/PS1/Tau三转基因小鼠的基因鉴定,鉴定后4组行Morris水迷宫实验检测认知功能,最后取4组小鼠海马部位组织用Western-blot方法检测P-Tau(Ser396)和P-Tau(Thr231)蛋白的表达,了解各组小鼠Tau蛋白磷酸化水平情况。结果 AD模型组和AD胃旁路手术组的小鼠均携带APP、PS1及Tau3种基因,即为APP/PS1/Tau三转基因小鼠,造模成功。在水迷宫定位航行实验中,AD胃旁路手术组小鼠较AD模型组平均逃避潜伏期明显缩短(P<0.01),而与WT正常对照组比较,AD胃旁路手术组逃避潜伏期延长(P<0.05);空间探索实验中,AD胃旁路手术组较AD模型组跨越平台次数明显增加(t=3.376,P=0.007)。AD胃旁路手术组小鼠较AD模型组Tau蛋白磷酸化水平明显降低(P<0.01)。结论 胃旁路手术能明显改善阿尔茨海默病模型小鼠的认知功能。Objective To observe the effect of gastric bypass surgery on the cognitive function of APP/PS1/Tau transgenic Alzheimer's disease model mice (AD model mice). Methods From February 2018 to March 2019, the offspring of APP/PS1/Tau transgenic mice were randomly divided into AD gastric bypass operation group ( n =6) and AD model group ( n =6), and C57 mice of the same age were randomly divided into WT normal group. Control group ( n =6), WT normal gastric bypass surgery group ( n =6). Two months after gastric bypass surgery, APP/PS1/Tau transgenic mice were identified. Morris water maze test was used to detect cognitive function in the four groups. The expression of P-Tau (Ser396) and P-Tau (Thr231) proteins in hippocampus tissues of four groups of mice were detected by Western blot to understand the phosphorylation level of Tau protein in each group. Results The mice in the AD model group and the AD gastric bypass surgery group carried the APP, PS1 and Tau genes, which were APP/PS1/Tau three transgenic mice, and the model was successful. In the water maze positioning experiment, the average escape latency of the AD gastric bypass surgery group was significantly shorter than that of the AD model group ( P <0.01), while the AD gastric bypass surgery group had an extended escape latency compared with the WT normal control group. P <0.05), in the space exploration experiment, the number of crossing platforms in the AD gastric bypass surgery group was significantly higher than that in the AD model group ( t =3.376, P = 0.007 );the AD gastric bypass surgery group was compared with the AD model group. The level was significantly reduced ( P < 0.01). Conclusion Gastric bypass surgery can significantly improve the cognitive function of Alzheimer's disease model mice.

关 键 词：阿尔茨海默病 胃旁路手术 认知功能 TAU蛋白磷酸化 小鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]