卢海龙,Chun Guang Li,李佳欣,等.跑台运动对胰岛素抵抗小鼠骨骼肌自噬及PI3K/Akt/mTOR信号通路的影响[J].中华物理医学与康复杂志,2026,48(2):112-118
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| 跑台运动对胰岛素抵抗小鼠骨骼肌自噬及PI3K/Akt/mTOR信号通路的影响 |
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| DOI：10.3760/cma.j.cn421666-20250421-00351 |
| 中文关键词: 高脂膳食 跑台运动 PI3K/Akt/mTOR 信号通路 自噬 |
| 英文关键词: High-fat diet Treadmill exercise PI3K/Akt/mTOR signaling pathway Autophagy |
| 基金项目:浙江省教育厅 2024 年度高等学校国内访问工程师项目 (FG2024169) |
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| 中文摘要: |
| 目的 观察跑台运动对高脂膳食诱导的胰岛素抵抗 (IR) 小鼠自噬及磷脂酰肌醇 3 - 激酶 (PI3K)/ 蛋白激酶 B (Akt)/ 哺乳动物雷帕霉素靶蛋白 (mTOR) 信号通路的影响。方法 选取 8 周龄健康雄性 C57BL/6 小鼠 24 只，8 只纳入健康对照组（对照组），余 16 只用高脂膳食建立 IR 模型。造模 12 周后，将 16 只 IR 小鼠随机分为模型安静组（模型组）及跑台运动组（运动组），每组 8 只。对照组给予普通膳食，模型组及运动组继续高脂膳食喂养；运动组以最大摄氧量（VO₂max）75% 强度进行跑台运动干预 12 周，对照组及模型组不运动。干预结束后，HE 染色观察骨骼肌病理改变，检测血清甘油三酯 (TC)、胆固醇 (TG) 含量，Western blot 检测骨骼肌组织 p-PI3K、p-Akt、p-mTOR、LC3-Ⅱ、LC3-Ⅰ、p62 及 Beclin-1 表达，分析自噬相关蛋白与 PI3K/Akt/mTOR 信号通路的相关性。结果 与对照组比较，模型组小鼠体重、空腹血糖、血清 TC 及 TG 水平显著增加（P<0.05），骨骼肌正常细胞数量减少、横纹肌模糊或空泡样改变等病理损伤，LC3-Ⅱ、Beclin-1 蛋白表达及 LC3-Ⅱ/LC3-Ⅰ 比值显著降低（P<0.05），p62、p-PI3K、p-Akt 及 p-mTOR 蛋白表达显著增加（P<0.05）。与模型组比较，运动组小鼠体重、血糖、血清 TC 及 TG 水平显著降低（P<0.05），骨骼肌病理损伤减轻，LC3-Ⅱ、LC3-Ⅱ/LC3-Ⅰ 及 Beclin-1 蛋白表达显著增加（P<0.05），p62、p-PI3K、p-Akt 及 p-mTOR 蛋白表达显著降低（P<0.05）。相关性分析显示，骨骼肌 LC3-Ⅱ/LC3-Ⅰ 比值与 p-mTOR 蛋白表达负相关（P<0.05），Beclin-1 与 p-PI3K 及 p-Akt 蛋白表达负相关（P<0.05）。结论 有氧跑台运动可有效改善高脂膳食诱导的小鼠骨骼肌病理改变及 IR，其机制可能与抑制 PI3K/Akt/mTOR 信号通路、进而促进自噬活性有关。 |
| 英文摘要: |
| Objective To observe any effect of treadmill exercise on autophagy and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in insulin-resistant (IR) mice. Methods A high-fat diet was used to induce insulin-resistance in 16 8-week-old C57BL/6 mice. Eight additional mice served as the healthy control group fed a normal diet. After 12 weeks the 16 mice were randomly divided into a sedentary group (the model group) and a treadmill exercise group (the exercise group), each of 8. All continued their former diets. The exercise group performed treadmill exercise at 75% of their maximum oxygen consumption, while the control group and the model group did not. After 12 weeks, hematoxylin-eosin (HE) staining was used to observe any pathological changes in the skeletal muscles. Enzyme colorimetry and enzyme-linked immunosorbent assays were employed to detect serum triglyceride (TC) and cholesterol (TG). Western blotting was conducted to detect the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR), autophagy microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ), autophagy microtubule-associated protein 1 light chain 3-Ⅰ (LC3-Ⅰ), SQSTM1 protein (p62), and autophagy effector protein 1 (Beclin-1) in skeletal muscles. The correlation between the expression of autophagy-related proteins and the PI3K/Akt/mTOR signaling pathway was quantified. Results (1) Compared with the control group, the average body weight, fasting blood glucose, TC and TG of the model group increased significantly. The number of normal cells in the skeletal muscle of the model group was significantly reduced, with blurred or vacuolated striated muscle, condensed and shrunken cell nuclei, widened or broken internal gaps in the muscle fiber, and disordered structure. The expression of LC3-Ⅱ, Beclin-1 protein and the ratio of LC3-Ⅱ to LC3-Ⅰ in the skeletal muscle of the model group had decreased significantly, but the expression of p62, p-PI3K, p-Akt and p-mTOR proteins had increased significantly compared to the control group. (2) Compared with the model group, the body weight, blood glucose, and serum TG and TC of the exercise group decreased significantly. The number of normal cells in the skeletal muscles increased significantly, blurring or vacuolation of the striated muscle was significantly less, and disorder in the tissue structure was significantly alleviated. The expression of LC3-Ⅱ, LC3-Ⅱ/LC3-Ⅰ and Beclin-1 protein in the skeletal muscle increased significantly, on average, while p62, p-PI3K, p-Akt and p-mTOR protein levels decreased significantly. (3) LC3-Ⅱ/LC3-Ⅰ in the skeletal muscle of all of the mice was negatively correlated with p-mTOR, and the expression of Beclin-1 was negatively correlated with p-PI3K and p-Akt. Conclusions Aerobic treadmill exercise effectively improves insulin resistance and the pathological changes in skeletal muscle, at least in mice. The mechanism may be related to the promotion of autophagy through inhibiting the PI3K/Akt/mTOR signaling pathway. |
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