中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (5): 1171-1183.doi: 10.12307/2026.023

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

有氧和抗阻运动改善肥胖相关认知障碍的作用机制

刘  煜1，雷森林2，周锦涛3，刘  辉4，李先辉5   

  1. 1湖北第二师范学院体育学院，湖北省武汉市   430205；吉首大学，2体育科学学院，5医学院，湖南省吉首市   416000；3武汉大学体育部，湖北省武汉市   430072；4长江大学医学部，湖北省荆州市   434000
  • 收稿日期:2024-11-27 接受日期:2025-01-17 出版日期:2026-02-18 发布日期:2025-06-25
  • 通讯作者: 李先辉，博士，教授，吉首大学医学院，湖南省吉首市 416000
  • 作者简介:刘煜，男，1989年生，安徽省蚌埠市人，汉族，硕士，讲师，主要从事高等体育教学与运动训练研究。
  • 基金资助:
    国家自然科学基金面上项目(82271514)，项目负责人：刘辉；国家自然科学基金项目(81860636)，项目负责人：李先辉

Mechanisms by which aerobic and resistance exercises improve obesity-related cognitive impairment

Liu Yu1, Lei Senlin2, Zhou Jintao3, Liu Hui4, Li Xianhui5   

  1. 1College of Physical Education, Hubei University of Education, Wuhan 430205, Hubei Province, China; 2College of Physical Education, 5College of Medicine, Jishou University, Jishou 416000, Hunan Province, China; 3Physical Education Department, Wuhan University, Wuhan 430072, Hubei Province, China; 4College of Medicine, Changjiang University, Jingzhou 434000, Hubei Province, China
  • Received:2024-11-27 Accepted:2025-01-17 Online:2026-02-18 Published:2025-06-25
  • Contact: Li Xianhui, MD, Professor, College of Medicine, Jishou University, Jishou 416000, Hunan Province, China
  • About author:Liu Yu, MS, Lecturer, College of Physical Education, Hubei University of Education, Wuhan 430205, Hubei Province, China
  • Supported by:
    the National Natural Science Foundation of China, Nos. 82271514 (to LH) and 81860636 (to LXH)

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摘要：


文题释义：
肥胖相关认知障碍：是一种发生在肥胖群体中的认知功能障碍，主要表现为注意力减退和认知控制障碍、记忆障碍、认知灵活性下降和执行能力下降，主要的病理特征为胰岛素抵抗、氧化应激、外周及中枢神经炎症、线粒体功能障碍及神经元衰老损伤等。
核因子κB通路：是细胞内调控免疫应答、炎症反应、细胞增殖与凋亡等生理过程的关键信号传导途径，该通路涉及多种蛋白质复合体。在静息状态下，核因子κB与核因子κB抑制蛋白结合在细胞质中，从而维持非活化状态。当细胞遭遇特定的刺激信号，如促炎细胞因子、氧化应激或病原体感染时，核因子κB抑制蛋白激酶复合体被激活，导致核因子κB抑制蛋白的磷酸化和降解，从而释放核因子κB使其转位至细胞核并调控靶基因的转录。这一过程涉及经典和非经典途径，前者依赖于核因子κB抑制蛋白激酶复合体的激活，而后者则涉及核因子κB诱导激酶和核因子κB抑制蛋白激酶α的激活，导致p100的降解和p52/RelB复合体的形成，核因子κB通路的复杂调控网络机制对于维持细胞内环境稳态及响应外界刺激至关重要。

背景：肥胖不仅与糖尿病、心血管疾病等代谢性疾病有关，还与认知功能下降、痴呆等神经退行性疾病的风险增加密切相关。研究发现，有氧运动和抗阻运动有助于改善肥胖相关认知障碍，然而治疗效果和相关作用机制尚不明确。
目的：探究有氧运动、抗阻运动对肥胖相关认知障碍小鼠神经中枢的保护作用及机制。
方法：48只8周龄C57BL/6J野生型雄性小鼠随机分为4组：对照组正常饲养20周；高脂组用高脂饲料(60%脂肪供能)饲养20周；有氧运动组高脂饲养12周后，有氧运动干预8周；抗阻运动组高脂饲养12周后，抗阻运动干预8周。运动干预结束后分别称量体质量，进行胰岛素耐量测试、葡萄糖耐量测试、新物体识别实验和Y迷宫实验；苏木精-伊红染色观察各组小鼠海马和皮质组织细胞形态；实时荧光定量PCR检测肿瘤坏死因子α和白细胞介素6 mRNA表达；Western blot检测Bax、Bcl-2、核因子κB、Cleaved Caspase-1、Caspase-3、突触蛋白1、脑源性神经营养因子蛋白表达。
结果与结论：①与对照组相比，高脂组小鼠体质量增加(P < 0.05)，并伴随胰岛素抵抗以及认知功能障碍发生，海马组织中核因子κB、Bax、Caspase-3、Cleaved Caspase-1蛋白表达显著增加(P < 0.05)，脑源性神经营养因子、突触蛋白1、Bcl-2蛋白表达显著降低(P < 0.05)，Bcl-2/Bax 比值显著降低(P < 0.05)，炎症因子肿瘤坏死因子α和白细胞介素6 mRNA表达显著增加(P < 0.05)。②与高脂组相比，有氧运动组小鼠上述指标均得到显著改善(P < 0.05)，而抗阻运动组小鼠体质量减轻、炎症因子肿瘤坏死因子α、白细胞介素6 mRNA表达显著降低(P < 0.05)、Caspase-3蛋白表达显著降低(P < 0.05)以及脑源性神经营养因子蛋白表达显著增加(P < 0.05)，其他指标无显著变化(P > 0.05)。综合以上结果发现，长期运动可通过降低肥胖小鼠胰岛素抵抗、下调核因子κB通路表达、减轻炎症反应、抑制神经元凋亡和改善突触可塑性产生神经保护作用，有效缓解肥胖相关认知功能障碍，其中有氧运动的治疗效果优于抗阻运动。
https://orcid.org/0009-0000-2987-886X (刘煜) 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 肥胖相关认知障碍, 核因子κB, 有氧运动, 抗阻运动, 神经炎症, 突触可塑性, 凋亡, 工程化组织构建

Abstract: BACKGROUND: Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease, but also closely related to the increased risk of cognitive decline, dementia and other neurodegenerative diseases. Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment, but their therapeutic effects and related mechanisms of action are still unclear.
OBJECTIVE: To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.
METHODS: Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups: a control group was fed normally for 20 weeks; a high fat group was fed with high fat diet (60% fat energy) for 20 weeks; an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise; and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise. After the exercise intervention, body mass was weighed, insulin tolerance and glucose tolerance were tested to evaluate insulin resistance, and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment. The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining. The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR, and the protein expressions of Bax , Bcl-2, nuclear factor-κB, Cleaved Caspase-1, Caspase-3, synapsin 1 and brain-derived neurotrophic factor were detected by western blot.
RESULTS AND CONCLUSION: (1) Compared with the control group, the body mass of mice increased in the high-fat group (P < 0.05), accompanied by insulin resistance and cognitive dysfunction, the expression levels of nuclear factor-κB, Bax, Caspase-3, Cleaved Caspase-1 in the hippocampus were significantly increased (P < 0.05), the expression levels of brain-derived neurotrophic factor, synapsin 1 and Bcl-2 proteins were significantly decreased (P < 0.05), Bcl-2/Bax ratio was significantly decreased (P < 0.05), and the mRNA levels of inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were significantly up-regulated (P < 0.05). (2) Compared with the high-fat group, the above indexes were significantly improved in the aerobic exercise group (P < 0.05), while in the resistance exercise group, the body mass of mice was significantly decreased, the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased (P < 0.05), the protein expression of Caspase-3 was significantly decreased (P < 0.05), and the protein expression of brain-derived neurotrophic factor was significantly up-regulated (P < 0.05), but no significant changes were observed in the other indexes (P > 0.05). In conclusion, long-term exercise can reduce insulin resistance, down-regulate the expression of nuclear factor-κB pathway, weaken inflammatory response, inhibit neuronal apoptosis and improve synaptic plasticity, resulting in neuroprotective effects, and effectively alleviate obesity-related cognitive dysfunction in obese mice. The therapeutic effect of aerobic exercise is superior to that of resistance exercise.


Key words: obesity-related cognitive impairment, nuclear factor-κB, aerobic exercise, resistance exercise, neuroinflammation, synaptic plasticity, apoptosis, engineered tissue construction

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