| 跑台运动通过p38信号上调FNDC5激活Akt改善Ⅱ型糖尿病小鼠认知功能障碍 |
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| 引用本文： | 张蒙,吴双双,郭源,寇现娟.跑台运动通过p38信号上调FNDC5激活Akt改善Ⅱ型糖尿病小鼠认知功能障碍[J].武汉体育学院学报,2022,56(4):72-80. |
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| 作者姓名： | 张蒙 吴双双 郭源 寇现娟 |
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| 作者单位： | 1.武汉体育学院 健康科学学院,湖北 武汉 430079
2.武汉体育学院 运动训练监控湖北省重点实验室,湖北 武汉 430079 |
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| 基金项目： | 国家自然科学基金项目(81601228)；;教育部人文社会科学研究规划基金项目(21YJA890014)； |
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| 摘 要： | 目的:探讨8周跑台运动对db/dbT2DM小鼠认知功能的影响及其分子机制。方法:24只8周龄db/dbT2DM小鼠和8只同龄对照m/m小鼠,将db/db小鼠随机分为:模型组(db/db)、运动干预组(db+Exe)、运动联合p38抑制剂组(db+Exe+SB203580)。db+Exe组进行8周跑台训练,db+Exe+SB203580组进行8周跑台运动联合SB203580抑制剂灌胃处理(5mg/kg,3d/W,8W)。每周定时检测小鼠的体重和空腹血糖;干预结束后,取全脑及海马组织,免疫组织化学染色观察海马不同区域的神经元损伤状态;Western Blot检测海马组织中AD样病理、神经炎症、突触可塑性、过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)/Ⅲ型纤连蛋白组件包含蛋白5(FNDC5)、Akt激酶等蛋白的表达。结果显示:(1)跑台运动可明显改善db/db小鼠的认知功能障碍。(2)减轻db/db小鼠的海马神经元损伤。(3)降低海马内AD样病理、神经炎症蛋白的表达,增加突触蛋白的表达水平。(4)通过p38信号上调PGC-1α/FNDC5的表达。(5)跑台运动可激活Akt激酶,而p38抑制剂可降低跑台运动对Akt激酶的激活作用。结论:8周跑台运动可明显改善db/db小鼠的认知功能障碍,其机制可能是通过p38上调PGC-1α/FNDC5,激活Akt激酶,减弱AD病理进程,降低炎性反应,增加突触可塑性,改善其空间学习记忆能力。
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| 关 键 词： | 运动医学 跑台运动 II型糖尿病 p38 PGC-1α/FNDC5 Akt激酶 认知功能障碍 |
| 收稿时间： | 2022-01-18 |
Treadmill Exercise Improves Cognitive Impairment in T2DM Mice by Relying on p38-Mediated FNDC5 Upregulation and Akt Activation |
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| ZHANG Meng,WU Shuangshuang,GUO Yuan,et al.Treadmill Exercise Improves Cognitive Impairment in T2DM Mice by Relying on p38-Mediated FNDC5 Upregulation and Akt Activation[J].Journal of Wuhan Institute of Physical Education,2022,56(4):72-80. |
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| Authors: | ZHANG Meng WU Shuangshuang GUO Yuan |
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| Institution: | School of Health Sciences, Wuhan Sports Univ., Wuhan 430079, China
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| Abstract: | To investigate the molecular mechanism of the effect of 8-week treadmill exercise on the cognitive function of db/db T2DM mice,24 SPF db/db T2DM mice 8 weeks old and 8 normal m/m mice of the same age were used.The db/db mice were randomly divided into model group (db/db),exercise intervention group (db+Exe) and combined exercise with p38 inhibitor group (db+Exe+SB203580).db+Exe group received 8-week treadmill exercise training,and db+Exe+SB203580 group received 8-week treadmill exercise combined with SB203580 inhibitor(5mg/kg,3d/W,8W).The weight and fasting blood glucose of the mice every were regularly determined every week.After the intervention,the whole brain and hippocampus of mice were taken.Immunohistochemical staining was used to evaluate the neuronal injury in different regions of hippocampus.Western Blot detected the expression of AD-like pathological proteins,neuroin flammation-related proteins,synaptic plasticity-related proteins,PGC-1α/FNDC5 and key proteins of AKT signaling in hippocampus tissues.The results showed that 8 weeks of treadmill exercise improved the cognitive impairment of db/db mice and reduced the damage of hippocampal neurons in db/db mice (especially CA3 area) and the loss of mature neurons.Treadmill running attenuated the expression of AD-like pathological proteins and inflammation related proteins and increased the level of synapse related proteins in hippocampus.Moreover,treadmill exercise up-regulated the expression of PGC-1α/FNDC5 through p38 signaling.Meanwhile,treadmill exercise could activate Akt kinase,while p38 inhibitor could reduce the activation of Akt.Taken together,8-week treadmill exercise could significantly improve the cognitive impairment of db/db mice.For the mechanism,treadmill running regulated PGC-1α/FNDC5 up and activated Akt kinase by relying on p38 signaling,weakened the pathological process of AD,reduced inflammatory response,increased synaptic plasticitynd,thus improved its spatial cognitive ability. |
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| Keywords: | sport medicine treadmill running type II diabetes p38 PGC-1α/FNDC5 Akt kinase cognitive dysfunction |
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