腫瘤壞死因子α對COPD 大鼠骨骼肌蛋白酶體C2 亞基表達的影響_《中國呼吸與危重監護雜志》

作者：

張悅 ,  徐衛國 , 羅勇 , 韓鋒鋒 , 楊天蕓 , 陳迎春

上海交通大學醫學院附屬新華醫院呼吸科（上海 200092）;

關鍵詞：

慢性阻塞性肺疾病腫瘤壞死因子α 骨骼肌蛋白泛素-蛋白酶體 C2亞基

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目的研究COPD 大鼠骨骼肌蛋白酶體C2 亞基的表達, 以及TNF-α對其表達的影響, 探討COPD 大鼠骨骼肌蛋白高分解代謝的機制。方法 SD 大鼠隨機分為對照組、COPD 組及COPD + TNF-α組, 每組15 只。COPD 組和COPD + TNF-α組大鼠用單純熏香煙法制成COPD 大鼠動物模型, 分離其伸趾長肌, 分別給予不含和含TNF-α( 10 μg/L) 的孵育液進行離體有氧孵育。利用實時定量 PCR 和Western blot 技術檢測C2 亞基在轉錄和蛋白水平的變化。結果 COPD 組和COPD + TNF-α 組C2 亞基mRNA 表達為對照組的1. 74 倍和1. 95 倍( P 均 lt; 0. 01) , 其中COPD + TNF-α組顯著高于 COPD 組( P lt;0. 01) 。COPD 組和COPD + TNF-α組C2 亞基蛋白表達也顯著高于對照組( 1. 04 ±0. 15 和1. 23 ±0. 16 比0. 71 ±0. 12, P lt;0. 05 和P lt; 0. 01) , COPD組和COPD + TNF-α組表達無顯著差異 ( P gt;0. 05) 。結論 COPD 時骨骼肌蛋白降解增加可能是經由TNF-α激活泛素-蛋白酶體途徑所致。

引用本文： 張悅,徐衛國,羅勇,韓鋒鋒,楊天蕓,陳迎春. 腫瘤壞死因子α對COPD 大鼠骨骼肌蛋白酶體C2 亞基表達的影響. 中國呼吸與危重監護雜志, 2009, 09(5): 436-440. doi: 復制

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21.	Schols AM. Pulmonary cachexia. Int J Cardiol, 2002, 85: 101-110.
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25.	徐衛國, 羅勇, 吳靖川, 等. 不同營養狀態COPD 腫瘤壞死因子- α測定及其臨床意義. 中國實用內科雜志, 1999, 19: 654-655.
26.	Ryther RCC, Flynt AS, Phillips 3rd JA, et al. siRNA therapeutics: big potential from small RNAs. Gene Ther, 2005, 12: 5-11.
27.	Tisdale MJ. The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting. J Support Oncol, 2005, 3: 209-217.
28.	年歐洲呼吸學會年會慢性阻塞性肺疾病研究進展. 中國呼吸與危重監護雜志, 2004, 3: 413-415.

1. Man WD, Moxham J, Polkey MI. Magnetic stimulation for the measurement of respiratory and skeletal muscle function. Eur Respir J, 2004, 24: 846-860.
2. 王曾禮. 更新對慢性阻塞性肺疾病認識的觀念. 中國呼吸與危重監護雜志, 2007, 6: 401-402.
3. 白沖. 慢性阻塞性肺疾病的危險因素、流行情況及未來發展趨勢. 中國呼吸與危重監護雜志,2007, 6: 403-405.
4. Schols AM. Nutritional and metabolic modulation in chronic obstructive pulmonary disease management. Eur Respir J Suppl, 2003, 46: 81s-86s.
5. 楊天蕓, 徐衛國, 羅勇, 等. 慢性阻塞性肺病大鼠骨骼肌蛋白降解的變化. 上海交通大學學報( 醫學版) , 2008, 28: 525-527.
6. Creutzberg EC, Schols AM, Weling-Scheepers CA, et al. Characterization of nonresponse to high caloric oral nutritional therapy in depleted patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2000, 161: 745-752.
8. 李紅梅, 崔德健, 佟欣, 等. 熏香煙加氣管注內毒素和單純熏香煙法建立大鼠COPD 模型. 中國病理生理雜志, 2002, 18: 808-812.
9. Celli BR, MacNee W, ATS /ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS /ERS position paper. Eur Respir J, 2004, 23: 932-946.
10. 姚婉貞, 陳亞紅.
11. , No.
12. Jagoe RT, Engelen MP. Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease. Eur Respir J Suppl, 2003, 46: 52s-63s.
13. Rutten EP, Franssen FM, Engelen MP, et al. Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease. Am J Clin Nutr, 2006, 83: 829-834.
14. Bargon J, Müller U, Buhl R. COPD, a systemic disease--nutritional approaches. Med Klin( Munich) , 2004, 99: 719-726.
15. 高福生, 潘全, 李淑蘭, 等. 慢性阻塞性肺疾病患者營養狀態對運動耐力及通氣氧耗的影響. 中國呼吸與危重監護雜志, 2004, 中國呼吸與危重監護雜志2009 年9 月第8 卷第5 期Chin J Respir Crit Care Med, September 2009, Vol.
16. Gao M, Karin M. Regulating the regulators: control of protein ubiquitination and ubiquitin-like modifications by extracellular stimuli. Mol Cell, 2005, 19: 581-593.
17. Taillandier D, Combaret L, Pouch MN, et al. The role of ubiquitinproteasome- dependent proteolysis in the remodelling of skeletal muscle. Proc Nutr Soc, 2004, 63: 357-361.
18. McKinnell IW, Rudnicki MA. Molecular mechanisms of muscle atrophy. Cell, 2004, 119: 907-910.
19. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 - △△ Ct method. Methods, 2001, 25: 402-408.
20. Adams V, Mangner N, Gasch A, et al. Induction of MuRF1 is essential for TNF-alpha-induced loss of muscle function in mice. J Mol Biol, 2008, 384: 48-59.
21. Schols AM. Pulmonary cachexia. Int J Cardiol, 2002, 85: 101-110.
22. Van Helvoort HA, Heijdra YF, Thijs HM, et al. Exercise-induced systemic effects in muscle-wasted patients with COPD. Med Sci Sports Exerc, 2006, 38: 1543-1552.
23. Sevenoaks MJ, Stockley RA. Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity--a common inflammatory phenotype? Respir Res, 2006, 7 : 70 .
24. Eid AA, Ioneseu AA, Nixon LS. Inflammatory Response and Body Composition in Chronic Obstructive Pulmonary Disease. AmJRespir Crit Care Meel Vol, 2001, 164: 1414-1418.
25. 徐衛國, 羅勇, 吳靖川, 等. 不同營養狀態COPD 腫瘤壞死因子- α測定及其臨床意義. 中國實用內科雜志, 1999, 19: 654-655.
26. Ryther RCC, Flynt AS, Phillips 3rd JA, et al. siRNA therapeutics: big potential from small RNAs. Gene Ther, 2005, 12: 5-11.
27. Tisdale MJ. The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting. J Support Oncol, 2005, 3: 209-217.
28. 年歐洲呼吸學會年會慢性阻塞性肺疾病研究進展. 中國呼吸與危重監護雜志, 2004, 3: 413-415.

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