中国临床解剖学杂志 ›› 2022, Vol. 40 ›› Issue (1): 39-44.doi: 10.13418/j.issn.1001-165x.2022.1.08

• 实验研究 • 上一篇    下一篇

中老年小鼠通过长期运动改善Aβ1-42诱导的认知功能障碍

张卫国, 杨娜, 杨静, 刘雪芹, 赵云鹤*   

  1. 山西医科大学人体解剖学教研室,  太原   030001
  • 收稿日期:2021-10-03 出版日期:2022-01-25 发布日期:2022-01-19
  • 通讯作者: 赵云鹤,博士,副教授,E-mail:yunhezhao@sxmu.edu.cn
  • 作者简介:张卫国(1978-),男,山西太原人,讲师,硕士,研究方向:神经系统疾病预防与控制,E-mail:13934588509@139.com
  • 基金资助:
    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)

Long-term exercise ameliorates cognitive disorder induced by Aβ1-42 in middle-aged and elderly mice

Zhang Weiguo, Yang Na, Yang Jing, Liu Xueqin, Zhao Yunhe*   

  1. Department of Human Anatomy, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2021-10-03 Online:2022-01-25 Published:2022-01-19

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(Aβ1-42)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),③Aβ1-42静坐对照组(AS),④Aβ1-42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Aβ1-42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Aβ1-42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Aβ1-42导致的认知功能障碍。

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

Abstract: Objective To observe the mechanism of cognitive dysfunction caused by Aβ-amyloid 1-42 (Aβ1-42) 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 Aβ1-42 sedentary group (AS),④an Aβ1-42 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 Aβ1-42 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 Aβ1-42 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 Aβ1-42 through long-term voluntary running wheel exercise. 

Key words: Middle-aged and elderly mice,  Long-term exercise,  Aβ1-42,  Proteasome activity, Cognitive dysfunction

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