Gao Haoyang, Ma Xiaotong, Wang Ze, Zhu Danlin, Guo Yifan, Zhao Linlin, Xiao Weihua
Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China.
School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Cells. 2025 Jul 4;14(13):1026. doi: 10.3390/cells14131026.
Diabetic lung disease, characterized by inflammation and fibrosis, is an emerging chronic complication of type 2 diabetes mellitus (T2DM). However, systematic studies on the effects of exercise interventions remain limited. This study aimed to investigate the impact of different exercise types (swimming, resistance training, and high-intensity interval training [HIIT]) on pulmonary inflammation and fibrosis in T2DM mice, and to explore underlying molecular mechanisms. A T2DM mouse model was established by a high-fat diet (HFD) combined with streptozotocin (STZ) induction. Mice were randomly divided into sedentary control, swimming, resistance training, and HIIT groups, and underwent 8 weeks of exercise intervention. After the intervention, body composition was assessed. Lung histopathological changes were evaluated by hematoxylin&eosin (HE) and Masson staining. Inflammatory cytokines, fibrosis markers, and the expression of the TGF-β1/Smad signaling pathway were detected. Macrophage infiltration and polarization were also analyzed. Exercise intervention improved body composition and reduced oxidative stress in T2DM mice. All three exercise modalities downregulated inflammatory cytokine expression, inhibited macrophage activation and M1 polarization, and promoted M2 polarization. Additionally, exercise improved lung tissue structure, reduced collagen deposition, and decreased the expression of fibrosis-related markers. Furthermore, anti-fibrotic effects were mediated by suppression of the TGF-β1/Smad signaling pathway and inhibition of epithelial-mesenchymal transition (EMT). Among the interventions, HIIT demonstrated the strongest inhibitory effect on the TGF-β1/Smad pathway, while swimming showed the most significant anti-inflammatory benefits. Different types of exercise effectively alleviate pulmonary inflammation and fibrosis in T2DM mice. These effects are closely related to the inhibition of oxidative stress, regulation of macrophage polarization, and suppression of TGF-β1/Smad signaling activation, with swimming and HIIT demonstrating superior protective benefits.
糖尿病性肺病以炎症和纤维化为特征，是2型糖尿病（T2DM）新出现的一种慢性并发症。然而，关于运动干预效果的系统性研究仍然有限。本研究旨在探讨不同运动类型（游泳、抗阻训练和高强度间歇训练[HIIT]）对T2DM小鼠肺部炎症和纤维化的影响，并探索其潜在的分子机制。通过高脂饮食（HFD）联合链脲佐菌素（STZ）诱导建立T2DM小鼠模型。将小鼠随机分为久坐对照组、游泳组、抗阻训练组和HIIT组，并进行为期8周的运动干预。干预后，评估身体成分。通过苏木精-伊红（HE）染色和Masson染色评估肺组织病理学变化。检测炎症细胞因子、纤维化标志物以及TGF-β1/Smad信号通路的表达。还分析了巨噬细胞浸润和极化情况。运动干预改善了T2DM小鼠的身体成分并降低了氧化应激。所有三种运动方式均下调了炎症细胞因子的表达，抑制了巨噬细胞活化和M1极化，并促进了M2极化。此外，运动改善了肺组织结构，减少了胶原沉积，并降低了纤维化相关标志物的表达。此外，抗纤维化作用是通过抑制TGF-β1/Smad信号通路和抑制上皮-间质转化（EMT）介导的。在这些干预措施中，HIIT对TGF-β1/Smad通路的抑制作用最强，而游泳显示出最显著的抗炎益处。不同类型的运动可有效减轻T2DM小鼠的肺部炎症和纤维化。这些作用与抑制氧化应激、调节巨噬细胞极化以及抑制TGF-β1/Smad信号激活密切相关，其中游泳和HIIT显示出更好的保护作用。
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