基于Chemerin-RhoA/ROCK通路研究运动改善COPD膈肌功能障碍的作用机制

膈肌功能障碍是严重影响慢性阻塞性肺疾病（COPD）患者呼吸功能与生活质量的突出肺外损伤效应。目前研究显示运动训练对COPD膈肌功能障碍有改善作用，但其作用机制有待进一步深入探究。项目团队前期研究发现，chemerin参与了运动训练调节系统性炎症改善COPD膈肌功能的过程，但运动如何通过chemerin调节系统性炎症、以及该调节作用是否与chemerin异构体表达相关还不是十分清楚。因此，本项目将聚焦chemerin下游信号RhoA/ROCK及chemerin异构体，通过跑台运动训练并结合chemerin异构体重组蛋白干预ROCK基因敲除COPD小鼠、机械应力刺激COPD膈肌细胞，从分子和细胞水平观察运动是否通过Chemerin-RhoA/ROCK减轻炎症反应，改善COPD膈肌功能障碍。项目研究开展有助于部分揭示运动防治COPD膈肌功能障碍的作用机制，为COPD临床肺康复防治干预提供新思路。

Diaphragm dysfunction is one of the extrapulmonary effects that seriously affects respiratory function and quality of life in patients with Chronic Obstructive Pulmonary Disease (COPD). Current research demonstrate that exercise training can improve diaphragm dysfunction of COPD, but its mechanism needs further investigation. Previous research from our project team have been demonstrated that chemerin participated in the process of exercise training regulating systemic inflammation to improve the diaphragm function of COPD, but it is still unclear how exercise regulates systemic inflammation through chemerin and whether this regulation is related to the expression of chemerin isoforms. Therefore, this project focuses on the downstream signal of chemerin, RhoA/ROCK and chemerin isoforms, intervenes in ROCK gene knockout COPD mice by treadmill training and combined with chemerin isoforms recombinant proteins, and stimulates COPD diaphragm muscle cells by mechanical stress, to investigate whether exercise can reduce inflammation and improve COPD diaphragm dysfunction through Chemerin-RhoA/ROCK at the molecular and cellular level. The research benefits to partially reveal the mechanism of exercise improving the diaphragm dysfunction of COPD, and provide theoretical basis to some extent for the clinical pulmonary rehabilitation in COPD.