Murf1与CFL2在慢性阻塞性肺疾病患者外周血中的表达及其相关性研究

Study on expression of Murf1 and CFL2 in peripheral blood of patients with chronic obstructive pulmonary disease and their correlation

中文关键词: 肺疾病  慢性阻塞性  肌肉萎缩相关泛素连接酶1  肌动蛋白解聚因子-2  肌萎缩

英文关键词: chronic obstructive pulmonary disease  muscle atrophy-related ubiquitin ligase 1  cofilin-2  muscular atrophy

中文摘要:

      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.

英文摘要:

      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.