【摘要】 目的 探讨肌肉萎缩相关泛素连接酶1(Murf1)及肌动蛋白解聚因子-2(CFL2)在慢性阻塞性肺疾病(COPD)患者外周血样本中表达的变化规律及其相关性，并验证Murf1对CFL2的调控作用。方法 纳入COPD患者20例为COPD组，以及同期健康体检者20名为对照组，收集血液样本并提取总RNA。使用实时荧光定量聚合酶链反应技术检测Murf1和CFL2的mRNA表达水平，并进行Pearson相关性分析。在马血清诱导的体外小鼠成肌细胞系C2C12肌肉萎缩模型中，通过Murf1过表达及干扰小RNA沉默处理，检测CFL2的蛋白表达变化。结果 与对照组相比，COPD组Murf1表达显著升高(P<0.001),而CFL2表达显著降低(P<0.001)。相关性分析显示，Murf1与CFL2的表达水平呈现负相关(r=-0.503 9,P<0.05)。体外细胞实验结果发现Murf1过表达导致CFL2蛋白水平下降，而Murf1沉默可恢复CFL2表达。结论 COPD患者外周血Murf1上调、CFL2下调，且两者呈负相关。Murf1可能通过抑制CFL2的表达参与COPD相关的肌肉萎缩过程，可能是治疗COPD患者骨骼肌功能障碍的潜在靶点。更多还原

【Abstract】 Objective To investigate the expression patterns of muscle atrophy-related ubiquitin ligase 1(Murf1) and actin-regulatory protein cofilin-2(CFL2) in peripheral blood samples from patients with chronic obstructive pulmonary disease(COPD) and their correlation, and validate the regulatory effect of Murf1 on CFL2. Methods Twenty COPD patients were enrolled as the COPD group, and twenty healthy individuals undergoing physical examinations during the same period served as the control group. Their blood samples were collected for total RNA extraction. The mRNA expression levels of Murf1 and CFL2 were measured by quantitative real-time PCR, and Pearson correlation analysis was performed.Additionally, in an in vitro muscle atrophy model of mouse myoblast cell line C2C12 induced by horse serum, the protein expression changes of CFL2 were detected through overexpression of Murf1 and knockdown of Murf1 with small interfering RNA. Results Compared with the control group, Murf1 expression increased significantly(P<0.001) and CFL2 expression decreased significantly(P<0.001) in the COPD group. Correlation analysis showed a negative correlation between the expression levels of Murf1 and CFL2(r=-0.503 9, P<0.05). In vitro cellular experiments revealed that Murf1 overexpression led to a decrease in CFL2 protein levels, while Murf1 knockdown restored CFL2 expression. Conclusion Murf1 is upregulated and CFL2 is downregulated in the peripheral blood of COPD patients, and their expressions are negatively correlated. Murf1 may be involved in COPD-associated muscle atrophy by inhibiting CFL2 expression.It suggests that it may be a potential target for the treatment of skeletal muscle dysfunction in patients with COPD.更多还原