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

目的探讨AKT／FOXOs／Atrogin-1／MuRFl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Westernblot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）。Westernblot分析结果显示，伸趾长肌组织中Atrogin一1的蛋白相对表达量COPD组较对照组明显增加（P〈0．01）；MuRFl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-AKTCOPD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。

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

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.