肿瘤坏死因子-α在慢阻肺大鼠骨骼肌蛋白分解代谢中的作用及其机制  

Effects of tumor necrosis factor-α on metabolism of skeletal muscle protein in rats with chronic obstructive pulmonary disease and underlying mechanisms

作　　者：张悦[1] 罗勇[1] 徐卫国[1] 

机构地区：[1]上海交通大学医学院新华医院呼吸科,上海200092

出　　处：《上海交通大学学报（医学版）》2008年第9期1126-1129,共4页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市自然科学基金(05ZR14063)~~

摘　　要：目的研究肿瘤坏死因子-α(TNF-α)在慢性阻塞性肺疾病(COPD)大鼠骨骼肌蛋白高分解代谢中的作用及其机制。方法45只SD大鼠随机分为空白对照组、COPD组和COPD+TNF-α组,每组15只。COPD组和COPD+TNF-α组大鼠用单纯熏香烟法制成COPD大鼠动物模型,分离其伸趾长肌,分别给予含或不含有TNF-α(10μg/L)的孵育液进行离体有氧孵育。实时定量PCR和Western blot检测泛素在mRNA和蛋白水平的变化。结果COPD组和COPD+TNF-α组泛素mRNA和蛋白的表达均高于空白对照组(P<0.05或P<0.01)。结论COPD时骨骼肌蛋白降解增加可能是TNF-α激活泛素-蛋白酶体途径所致。Objective To study the effects of tumor necrosis factor-α （TNF-α） on hypermetabolism of skeletal muscle protein in rats with chronic obstructive pulmonary disease （COPD） and explore the mechanisms. Methods Forty-five SD rats were randomly divided into normal control group, COPD group and COPD ＋ TNF-α group （ n = 15）. Rat COPD models were established by passive cigarette smoking in COPD group and COPD ＋ TNF-α group. After dissecting and isolating the extensor digitorium longus （EDL） muscles, the EDL muscles were either cultured with media containing 10 ug/L recombinant rat TNF-α or without TNF-α. The subsequent changes in ubiquitin mRNA and protein levels were determined by real-time quantitative PCR and Western blot, respectively. Results The expressions of ubiquitin mRNA and protein of COPD group and COPD ＋ TNF-α group were higher than those of normal control group （P 〈 0. 05 or P 〈 0. 01 ）. Conclusion The increase of protein degradation in COPD may be caused by TNF-α through strengthening the function of ubiquitin-dependent proteolytic system.

关 键 词：慢性阻塞性肺疾病 肿瘤坏死因子-Α 骨骼肌蛋白 泛素-蛋白酶体 大鼠 

分 类 号：R563.9[医药卫生—呼吸系统]