Department of Sports Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
J Cell Mol Med. 2023 Nov;27(21):3217-3234. doi: 10.1111/jcmm.17879. Epub 2023 Jul 30.
This study aims to analyse the pathological features of skeletal muscle injury repair by using rats to model responses to different exercise intensities. Eighty-four rats were randomly divided into five groups for treadmill exercise. The short-term control, low-intensity, medium-intensity and high-intensity groups underwent gastrocnemius muscle sampling after 6, 8 and 12 weeks of exercise. The long-term high-intensity group underwent optical coherence tomography angiography and sampling after 18 weeks of exercise. RNA sequencing was performed on the muscle samples, followed by the corresponding histological staining. Differentially expressed genes were generally elevated at 6 weeks in the early exercise stage, followed by a decreasing trend. Meanwhile, the study demonstrated a negative correlation between time and the gene modules involved in vascular regulation. The modules associated with muscle remodelling were positively correlated with exercise intensity. Although the expression of many genes associated with common angiogenesis was downregulated at 8, 12 and 18 weeks, we found that muscle tissue microvessels were still increased, which may be closely associated with elevated sFRP2 and YAP1. During muscle injury-remodelling, angiogenesis is characterized by significant exercise time and exercise intensity dependence. We find significant differences in the spatial distribution of angiogenesis during muscle injury-remodelling, which be helpful for the future achievement of spatially targeted treatments for exercise-induced muscle injuries.
本研究旨在通过使用大鼠模型来分析不同运动强度下骨骼肌损伤修复的病理特征。84 只大鼠被随机分为五组进行跑步机运动。短期对照组、低强度组、中强度组和高强度组在运动 6、8 和 12 周后进行比目鱼肌取样。长期高强度组在运动 18 周后进行光相干断层扫描血管造影和取样。对肌肉样本进行 RNA 测序,然后进行相应的组织学染色。在早期运动阶段,差异表达基因通常在 6 周时普遍升高,随后呈下降趋势。同时,研究表明,时间与参与血管调节的基因模块之间呈负相关。与肌肉重塑相关的模块与运动强度呈正相关。尽管许多与常见血管生成相关的基因在 8、12 和 18 周时表达下调,但我们发现肌肉组织微血管仍然增加,这可能与 sFRP2 和 YAP1 的升高密切相关。在肌肉损伤重塑过程中,血管生成具有显著的运动时间和运动强度依赖性。我们发现肌肉损伤重塑过程中血管生成的空间分布存在显著差异,这有助于未来实现针对运动引起的肌肉损伤的空间靶向治疗。