中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (10): 2449-2458.doi: 10.12307/2026.646

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

跑台运动改善糖尿病小鼠昼夜节律紊乱的代谢-认知障碍

李庆新1，张国栋2，魏思昂3，4，谢艳丽2   

  1. 1宜宾学院体育与大健康学院，四川省宜宾市  644000；山西农业大学，2体育部，3生命科学学院，山西省晋中市  030801；4复旦大学附属中山医院，上海市  200032
  • 收稿日期:2025-05-15 接受日期:2025-06-23 出版日期:2026-04-08 发布日期:2025-08-28
  • 通讯作者: 张国栋，博士，副教授，山西农业大学体育部，山西省晋中市 030801
  • 作者简介:李庆新，1990年生，山东省聊城市人，汉族，2015年四川大学毕业，硕士，讲师，主要从事体育教学与训练、运动健康与促进的研究。
  • 基金资助:
    首批国家体育科普基地项目(GJTK024)，项目负责人：张国栋；山西省省筹资金资助回国留学人员科研项目(2022-122)，项目负责人：张国栋

Treadmill exercise improves metabolic-cognitive impairment of circadian rhythm disorder in diabetic mice

Li Qingxin1, Zhang Guodong2, Wei Siang3, 4, Xie Yanli2   

  1. 1School of Physical Education and Health, Yibin University, Yibin 644000, Sichuan Province, China; 2Department of Physical Education, 3College of Life Sciences, Shanxi Agricultural University, Jinzhong 030801, Shanxi Province, China; 4Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China 
  • Received:2025-05-15 Accepted:2025-06-23 Online:2026-04-08 Published:2025-08-28
  • Contact: Zhang Guodong, PhD, Associate professor, Department of Physical Education, Shanxi Agricultural University, Jinzhong 030801, Shanxi Province, China
  • About author:Li Qingxin, MS, Lecturer, School of Physical Education and Health, Yibin University, Yibin 644000, Sichuan Province, China
  • Supported by:
    the First-batch National Sports Science Popularization Base Project, No. GJTK024 (to ZGD); Shanxi Province Provincial Scientific Research Project for Returned Overseas Students, No. 2022-122 (to ZGD)

PDF

0

摘要：


文题释义：
昼夜节律紊乱：是指生物体内源性生物钟与外界环境的光暗周期出现长期不匹配的状态。生物钟由下丘脑视交叉上核调控，通过调节褪黑素分泌、体温波动和激素释放等维持24 h生理节律。现代生活方式(如夜间过度光照、轮班工作、跨时区旅行)或病理因素(如神经退行性疾病)可导致昼夜节律失同步。这种紊乱会引发睡眠-觉醒周期异常、代谢综合征风险增加(如血糖失调、肥胖)、免疫力下降及情绪障碍。
代谢-认知障碍：指代谢功能障碍与认知损害相互作用的病理状态，表现为胰岛素抵抗、脂代谢异常等代谢紊乱与记忆减退、执行功能下降等认知缺陷并存，其核心机制涉及能量代谢失调引发脑内葡萄糖利用障碍，导致神经元线粒体功能受损和突触可塑性下降。慢性炎症状态和血脑屏障通透性改变促使脂肪因子、炎性细胞因子进入中枢神经系统，加剧β-淀粉样蛋白沉积和tau蛋白过度磷酸化。

背景：昼夜节律紊乱加剧胰岛素抵抗和糖脂代谢异常，成为糖尿病及其并发症的重要诱因。规律的有氧运动可通过激活AMPK信号通路增强胰岛素敏感性，同时上调沉默信息调节因子1表达以稳定核心时钟基因的节律性振荡。
目的：探究跑台运动对糖尿病小鼠昼夜节律紊乱诱导的代谢异常及认知功能障碍的改善作用，并分析其潜在分子机制。
方法：实验分为6组，8周龄野生型C57BL/6J小鼠与糖尿病db/db小鼠分别为正常对照组和糖尿病对照组，通过间歇性光照法(8 h光照/4 h黑暗，持续6周)建立昼夜节律紊乱模型，分别为模型组，糖尿病+模型组，并在建模的基础上实施6周跑台运动，分别为模型+运动组，糖尿病+模型+运动组。干预0，3，6周后检测小鼠体质量、血清褪黑素、空腹血糖、胰岛素抵抗的稳态模型评估(HOMA-IR)、葡萄糖耐量测试和胰岛素耐量测试、脂肪质量、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和Morris水迷宫行为学表现，以及胰腺组织BMAL1、CLOCK、Nrf2、超氧化物歧化酶2、沉默信息调节因子1和糖原合成酶激酶3β的mRNA表达水平。
结果与结论：①昼夜节律紊乱显著加剧db/db小鼠体质量增长、血清褪黑素水平降低、空腹血糖升高及脂质代谢异常，而运动干预使上述指标降低，并改善昼夜节律紊乱小鼠的糖耐量和胰岛素敏感性，显著降低白细胞介素4和升高干扰素γ水平(P < 0.01)；②运动能下调昼夜节律紊乱小鼠昼夜节律核心基因BMAL1、CLOCK表达，激活Nrf2-超氧化物歧化酶2抗氧化通路，并调控沉默信息调节因子1-糖原合成酶激酶3β信号轴；③运动干预使db/db小鼠逃逸潜伏期降低、穿越平台次数增加(P < 0.01)；④结果表明，跑台运动通过调控沉默信息调节因子1-糖原合成酶激酶3β信号轴及抗氧化通路，有效改善糖尿病小鼠昼夜节律紊乱引发的代谢异常、免疫失衡与认知损伤。  
https://orcid.org/0009-0006-4651-501X(李庆新)

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: 跑台运动, 沉默信息调节因子1, 糖原合成酶激酶3β, 糖尿病小鼠, 昼夜节律紊乱, 代谢异常, 认知功能障碍

Abstract: BACKGROUND: Disturbance of circadian rhythm aggravates insulin resistance and abnormal glucose and lipid metabolism, becoming an important inducement for diabetes and its complications. Regular aerobic exercise enhances insulin sensitivity through activation of the AMPK signaling pathway while upregulating silent information regulation 1 (SIRT1) expression to stabilize rhythmic oscillations of core clock genes.
OBJECTIVE: To explore the effect of treadmill exercise on metabolic abnormalities and cognitive dysfunction induced by circadian rhythm disturbance in diabetic mice, and analyze its underlying molecular mechanism. 
METHODS: The 8-week-old wild-type C57BL/6J and diabetic db/db mice were selected as normal controls and diabetic controls. Circadian rhythm disorder models were established by intermittent light (8-hour light/4-hour dark, lasting for 6 weeks), and divided into model and diabetes+model groups. Based on a 6-week treadmill exercise, mouse models were divided into model+exercise group and diabetes+model+exercise group. The detection indicators include body mass, serum melatonin, fasting blood glucose, homeostatic model assessment of insulin resistance, glucose tolerance test and insulin tolerance test, fat mass, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and Morris water maze behavioral performance, as well as BMAL1, CLOCK, Nrf2, superoxide dismutase 2, and mRNA expression levels of SIRT1 and glycogen synthase kinase 3β (GSK3β) in pancreatic tissues. 
RESULTS AND CONCLUSION: (1) Circadian rhythm disruption significantly exacerbated body mass gain, decreased serum melatonin levels, elevated fasting blood glucose, and abnormal lipid metabolism in db/db mice, while exercise intervention reduced these indicators, improved glucose tolerance and insulin sensitivity, significantly reduced the level of interleukin-4 and elevated the level of interferon-γ in mice with circadian rhythm disorders (P < 0.01). (2) Exercise downregulated the expression of the circadian core genes BMAL1 and CLOCK, activated the Nrf2-superoxide dismutase 2 antioxidant pathway, and regulated the SIRT1-GSK3 β signaling axis. (3) Exercise intervention decreased the escape latency and increased crossing platform frequency of db/db mice (P < 0.01). Overall, by regulating SIRT1-GSK3 β signal axis and antioxidant pathway, treadmill exercise can effectively improve metabolic abnormalities, immune imbalance and cognitive damage caused by circadian rhythm disorder in diabetic mice.

Key words: treadmill exercise, silent information regulation 1, glycogen synthase kinase 3β, diabetic mice, circadian rhythm disorder, metabolic abnormalities, cognitive dysfunction

中图分类号: