AKT/FOXOs/Atrogin-1/MuRF1信号通路在慢性阻塞性肺疾病大鼠骨骼肌萎缩中的作用  

Role of AKT/FOXOs/Atrogin-1/MuRF1 Signalling Pathway in Skeletal Muscle Atrophy in COPD Rats

作　　者：韩锋锋[1] 徐卫国[1] 崔志磊[1] 刘乾[1] 杨天芸[1] 张悦[1] 罗勇[1] 

机构地区：[1]上海交通大学医学院附属新华医院呼吸科,上海200092

出　　处：《中国呼吸与危重监护杂志》2013年第3期217-222,共6页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：上海市卫生局科研课题基金资助项目(编号:2010089)

摘　　要：目的探讨AKT/FOXOs/Atrogin-1/MuRF1信号通路在慢性阻塞性肺疾病(COPD)大鼠骨骼肌萎缩中的作用。方法采用单纯熏香烟法复制COPD大鼠动物模型。采用逆转录-聚合酶链式反应(RT-PCR)和Western blot技术检测COPD大鼠伸趾长肌内E3连接酶的两个肌肉萎缩特异性指标Atrogin-1和MuRF1,以及其上游FOXOs转录因子的基因与蛋白表达的变化;对伸趾长肌中磷酸化AKT(p-AKT)的蛋白表达及其与总AKT(t-AKT)的蛋白表达比率进行测定。结果 RT-PCR分析结果显示,COPD大鼠伸趾长肌组织中的Atrogin-1的mRNA表达明显上调(P<0.01);MuRF1和FOXO-1的mRNA表达与对照组比较差异有统计学意义(P<0.05)。Western blot分析结果显示,伸趾长肌组织中Atrogin-1的蛋白相对表达量COPD组较对照组明显增加(P<0.01);MuRF1的蛋白表达COPD组较对照组增加(P<0.05);FOXO-1的蛋白表达两组比较无明显差异(P>0.05)。COPD组大鼠伸趾长肌中p-AKT的蛋白表达较对照组增加(P<0.05),p-AKT/t-AKT COPD组明显高于对照组(P<0.01)。结论 AKT/FOXOs/Atrogin-1/MuRF1信号通路参与COPD骨骼肌萎缩机制并发挥重要作用。Objective To investigate the role of AKT/FOXOs/atrogin-1/MuRF1 signaling pathway in skeletal muscle atrophy in rats with chronic obstructive pulmonary diseases （COPD）. Methods Passive cigarette smoking was used to establish COPD model. The protein expression of atrogin-1, MuRF1, FOXO-1, phosohorylated-AKT and total AKT were measured by Western blot. The mRNA expression of atrogin-1, MuRF1 and FOXO-1 were measured by reverse transeription-polymerase chain reaction （RT-PCR）. Results Compared with the control group, the mRNA expressions of atrogin-1, MuRF1 and FOXO-1 significantly increased in extensor digitorum longus （EDL） of the COPD group （ P 〈 0. 05 ）. Meanwhile the protein expression of atrogin-1 and MuRF1 significantly increased in the COPD group（ P 〈 0.05 ）,while the protein expression of FOXO-I was not significantly different between two groups （P 〉 0. 05 ）. In addition,, the protein expression of phosohorylated-AKT and the ratio of phosohorylated-AKT to total AKT significantly increased in EDL of the COPD group （ P 〈 0. 05 ）. Conclusion The mRNA and protein expression of AKT/FOXOs/ atrogin-1/MuRF1 in skeletal muscle are significantly increased in COPD rats, suggesting that AKT/FOXOs/ atrogin-1/MuRF1 signalling pathway plays a crucial role in skeletal muscle atrophy of COPD.

关 键 词：慢性阻塞性肺疾病 AKT/FOXOs/Atrogin-1/MuRF1信号通路 大鼠 骨骼肌 萎缩 

分 类 号：R563.9[医药卫生—呼吸系统]