中老年小鼠通过长期运动改善Aβ_(1-42)诱导的认知功能障碍  

Long-term exercise ameliorates cognitive disorder induced by Aβ_(1-42) in middle-aged and elderly mice

作　　者：张卫国[1] 杨娜[1] 杨静[1] 刘雪芹[1] 赵云鹤[1] Zhang Weiguo;Yang Na;Yang Jing;Liu Xueqin;Zhao Yunhe(Department of Human Anatomy,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学人体解剖学教研室,太原030001

出　　处：《中国临床解剖学杂志》2022年第1期39-43,共5页Chinese Journal of Clinical Anatomy

基　　金：国家自然科学基金项目(81571381);山西省回国留学人员科研资助项目(2020-085);山西省青年科技研究基金(201801D221407);山西省高等学校教学改革创新项目(J2020094)。

摘　　要：目的观察中老年小鼠通过长期自主跑轮运动改善β淀粉样蛋白1-42(Aβ_(1-42))所致认知功能障碍及其机制。方法中老年BABL/c小鼠(12月龄)随机分为4组,①溶剂对照静坐组(VS),②溶剂对照长期自主跑轮运动组(VR),③Aβ_(1-42)静坐对照组(AS),④Aβ_(1-42)长期自主跑轮运动组(AR),按分组条件分别予以自主跑轮或静坐6个月,双侧海马注射Aβ_(1-42)或等量溶剂。注射两周后进行相关检测。结果Western blot显示中老年小鼠长期运动致海马泛素化蛋白下降0.2倍(P<0.05)。新物体识别实验显示AR组新物体识别指数高于AS组0.42倍(P<0.05);Y迷宫自发交替实验显示AR组的入臂正确率较AS组升高0.21倍(P<0.05)。荧光分光光度检测显示AR组海马蛋白酶体活性高于AS组0.18倍(P<0.05);Western blot显示AR组小鼠海马泛素化蛋白沉积较AS组小鼠减少0.21倍(P<0.05);免疫组化结果显示AR组Aβ_(1-42)沉积减少(P<0.01)。结论中老年小鼠长期自主跑轮运动可维持海马蛋白酶体活性,改善Aβ_(1-42)导致的认知功能障碍。Objective To observe the mechanism of cognitive dysfunction caused by Aβ-amyloid 1-42(Aβ_(1-42))in middle-aged and elderly mice by long-term exercise.Methods 12-month-old BABL/c mice were randomly divided into the following four groups:①a vehicle control sedentary group(VS),②a vehicle control long-term voluntary running wheel exercise group(VR),③an Aβ_(1-42) sedentary group(AS),④an Aβ_(1-42) long-term voluntary running wheel exercise group(AR).Voluntary running wheel exercise or sedentary for 6 months was performed according to the grouping conditions.The bilateral hippocampus was injected with Aβ_(1-42) or equivalent solvent for 6 months.Tests were performed two weeks after injection.Results Western blotting results showed that the accumulation of ubiquitinated protein in the hippocampus of 12-month-old BABL/c mice after long-term voluntary exercise was significantly lower than that in the sedentary group by about 0.2 times(P<0.05).The novel object recognition experiment showed that the preference index in the AR group was 0.42 times higher than that in the AS group(P<0.05).The spontaneous alternation experiment of Y maze showed that the correct rate of arm entry in AR group increased than that in AS group by about 0.21 times(P<0.05).The proteasome activity of AR hippocampus was significantly higher than that of AS group by about 0.18 times(P<0.05).Western blotting results showed the accumulation of ubiquitinated protein in the hippocampus in the AR group was significantly lower than that of AS group by about 0.21 times(P<0.05).Immunohistochemical results showed that Aβ_(1-42) deposition in AR group was lesser(P<0.01).Conclusions Middle-aged and elderly mice can maintain hippocampal proteasome activity and improve the cognitive dysfunction caused by Aβ_(1-42) through long-term voluntary running wheel exercise.

关 键 词：中老年小鼠 长期运动 β淀粉样蛋白1-42 蛋白酶体活性 认知障碍 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学]