胰島素樣生長因子對COPD 大鼠膈肌凋亡的保護作用及對肺功能的影響_《中國呼吸與危重監護雜志》

作者：

 孫麗華 , 歐陽曉平 , 谷偉 , 譚焰 , 高景蓬

南京醫科大學附屬南京第一醫院呼吸科（江蘇南京 210006）;

關鍵詞：

慢性阻塞性肺疾病胰島素樣生長因子1 膈肌凋亡肺功能 Fas /FasL

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目的探討重組的人胰島素樣生長因子1( rhIGF-1) 對COPD 大鼠膈肌凋亡的保護作用, 并觀察其對肺功能的影響。方法 45 只雄性Wistar 大鼠隨機分為對照組、模型組和干預組, 每組 15 只。模型組和干預組大鼠置于煙霧濃度為5% 的密閉熏箱內( 每天30 min, 共28 d) , 第1 d 和第 14 d向氣管內注射脂多糖200 μg。干預組大鼠同時每日皮下注射rhIGF-1( 60 μg /100 g) 1 次, 持續 28 d。對照組不予特殊處理。第1、14、28 d 各組隨機取5 只大鼠處死, 測定各組離體膈肌的重量、細胞凋亡率、膈肌中Fas 基因及蛋白表達水平。第28 d 處死前測定各組大鼠的肺功能。結果 28 d 后模型組和干預組大鼠分鐘呼氣量( VE ) 、最大呼氣流速( PEF) 、深吸氣量( IC) 、第0. 3 s 用力呼氣容積 ( FEV0. 3 ) 及膈肌質量均較對照組下降( P lt;0. 05) 。干預組膈肌質量、IC 及VE 值高于模型組( P 均 lt; 0. 05) , PEF 和FEV0. 3 與模型組比較無顯著差異( P gt; 0. 05) 。第14 和28 d, 干預組膈肌細胞凋亡率、 Fas 基因及蛋白表達均低于模型組( P 均 lt;0. 05) , 仍高于對照組( P 均 lt; 0. 05) 。結論 Fas / FasL 介導的凋亡途徑參與了膈肌凋亡的發生, rhIGF-1 可能通過干預Fas / FasL 途徑減少膈肌凋亡, 在一定程度上改善COPD 大鼠的VE 和IC 值。

引用本文： 孫麗華,歐陽曉平,谷偉,譚焰,高景蓬. 胰島素樣生長因子對COPD 大鼠膈肌凋亡的保護作用及對肺功能的影響. 中國呼吸與危重監護雜志, 2009, 09(5): 441-445. doi: 復制

1.	Gosker HR, Wouters EF, van der Vusse GJ, et al. Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. Am J Clin Nutr, 2000, 71: 1033-1047.
2.	Ottenheijm CA, Heunks LM, Sieck GC, et al. Diaphragm dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 172: 200-205.
3.	Degens H, Swisher AK, Heijdra YF, et al. Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster. Am J Physiol Regul Integr Comp Physiol, 2007, 293: 135- 144.
4.	林建海, 楊玲, 魯慧敏. 精氨酸對慢性阻塞性肺疾病呼吸衰竭合并營養不良的作用. 中國呼吸與危重監護雜志, 2004, 3: 91-93.
5.	Pérez R, García-Fernández M, Díaz-Sánchez M, et al. Mitochondrial protection by low doses of insulin-like growth factor-Ⅰ in experimental cirrhosis. World J Gastroenterol, 2008, 14 : 2731 -2739 .
6.	宋一平, 崔德健, 茅培英, 等. 慢性阻塞性肺疾病大鼠模型的建立及藥物干預的影響. 中華內科雜志, 2000, 39: 556-557.
7.	紀勇, 陳國強, 黃斌, 等. Caspase 抑制劑對大鼠心肌缺血/ 再灌注損傷Fas /FasL 表達的影響. 中國微循環, 2009, 2: 102-104.
8.	Radell PJ, Eleff SM, Nichols DG. Effects of loaded breathing and hypoxia on diaphgram metabolism as measured by ( 31 ) P-NMP spectroscopy. Appl Physiol, 2000, 88: 933-938.
9.	Barreiro E, de la Puente B, Minguella J, et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005 , 171: 1116 - 1124.
10.	Fournier M, Huang ZS, Li H, et al. Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters. Am J Physiol Regul Integr Comp Physiol, 2003, 285: R34-R43.
11.	Diaz O, Villafranca C, Ghezzo H, et al. Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest. Eur Respir J, 2000, 16: 269-275.
12.	O′Donnell DE, Forkert L, Webb KA. Evaluation of bronchodilator responses in patients with “irreversible”emphysema. Eur Respir J, 2001, 18: 914-920.
13.	Boni E, Corda L, Franchini D, et al. Volume effect and exertional dyspnoea after bronchodilator in COPD patients with and without expiratory flow limitation at rest. Thorax, 2002, 57: 528-532.
14.	Marin JM, Carrizo SJ, Gascon M, et al. Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001, 163: 1395-1399.

1. Gosker HR, Wouters EF, van der Vusse GJ, et al. Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. Am J Clin Nutr, 2000, 71: 1033-1047.
2. Ottenheijm CA, Heunks LM, Sieck GC, et al. Diaphragm dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 172: 200-205.
3. Degens H, Swisher AK, Heijdra YF, et al. Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster. Am J Physiol Regul Integr Comp Physiol, 2007, 293: 135- 144.
4. 林建海, 楊玲, 魯慧敏. 精氨酸對慢性阻塞性肺疾病呼吸衰竭合并營養不良的作用. 中國呼吸與危重監護雜志, 2004, 3: 91-93.
5. Pérez R, García-Fernández M, Díaz-Sánchez M, et al. Mitochondrial protection by low doses of insulin-like growth factor-Ⅰ in experimental cirrhosis. World J Gastroenterol, 2008, 14 : 2731 -2739 .
6. 宋一平, 崔德健, 茅培英, 等. 慢性阻塞性肺疾病大鼠模型的建立及藥物干預的影響. 中華內科雜志, 2000, 39: 556-557.
7. 紀勇, 陳國強, 黃斌, 等. Caspase 抑制劑對大鼠心肌缺血/ 再灌注損傷Fas /FasL 表達的影響. 中國微循環, 2009, 2: 102-104.
8. Radell PJ, Eleff SM, Nichols DG. Effects of loaded breathing and hypoxia on diaphgram metabolism as measured by ( 31 ) P-NMP spectroscopy. Appl Physiol, 2000, 88: 933-938.
9. Barreiro E, de la Puente B, Minguella J, et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005 , 171: 1116 - 1124.
10. Fournier M, Huang ZS, Li H, et al. Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters. Am J Physiol Regul Integr Comp Physiol, 2003, 285: R34-R43.
11. Diaz O, Villafranca C, Ghezzo H, et al. Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest. Eur Respir J, 2000, 16: 269-275.
12. O′Donnell DE, Forkert L, Webb KA. Evaluation of bronchodilator responses in patients with “irreversible”emphysema. Eur Respir J, 2001, 18: 914-920.
13. Boni E, Corda L, Franchini D, et al. Volume effect and exertional dyspnoea after bronchodilator in COPD patients with and without expiratory flow limitation at rest. Thorax, 2002, 57: 528-532.
14. Marin JM, Carrizo SJ, Gascon M, et al. Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001, 163: 1395-1399.

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