胰岛素样生长因子-I在慢性阻塞性肺疾病小气道的表达

Significance of insulin like growth factor-I express in small airway remodeling of rats with chronic obstructive pulmonary disease

目的探讨胰岛素样生长因子-I(IGF-I)在慢性阻塞性肺疾病(COPD)小气道的表达与平滑肌增厚、粘膜下层胶原沉积等导致气道重构的关系。方法制备COPDWistar大鼠模型10只,正常对照组10只,用免疫组织化学方法显示IGF-I在小气道的表达,用HE染色及masson三色染色显示气道平滑肌;用图像分析仪对IGF-I进行定量分析。结果COPD组IGF-I在小气道上皮细胞、粘膜下层、平滑肌层的表达均较对照组显著增高(P<0.01),地塞米松有一定的抑制作用(P<0.05);细支气管肺组织IGF-I表达与最大呼气流量(PEF)和0.3s用力呼气容积(FEV0.3)及FEV0.3/FVC(%)显著负相关,r值分别为-0.496(P<0.05),-0.487(P<0.05),-0.707(P<0.01)。IGF-I表达与小气道管壁厚度明显相关,r值为0.772(P<0.01)。结论COPD大鼠小气道存在气道重构及在小气道上皮细胞、粘膜下层及平滑肌层均有较丰富的IGF-I的表达,显示IGF-I在COPD小气道重构中起揭示作用及地塞米松对COPD小气道重构有预防作用。

Objective To assess whether insulin- llke growth factor- I（IGF- I）, a fibrogenic growth factor, involves in airway wall remodeling in chronic obstructive pulmonary disease（COPD）. Methods The male Wistar rats, weighed 280 ＋ 20g, were divided into tree groups： COPD group （n = 10）,normal control group（n = 10）.Expression of IGF- I were identified using immunohistochemistry on paraffin slides. Smooth muscles were identified using H- E stain and Massen＇s trichrome stain. Masson＇ s trichrome stain also used to determine collagen deposition in the small airways. The following parameters with a computerized image analysis system were measured in small airways cut in reasonable cross - sections. IGF - I was quantitatively analyzed. Results 1. Smooth muscle and collagen： Small airway wall thickness were prominent increased in COPD group （ P 〈 0.01 ）. ; 2. The negative correlationswere observed between the levels and lung function parameters ： In small airway, the expression of IGF - I was correlated negatively with PEF （r = - 0.496, P 〈 0.05）, FEV0.3 （ r = - 0.487, P 〈 0.05） and FEV0.3/FVC （ % ） （ r = - 0.707, P 〈 0.01 ）. The positive correlation was observed between the expresson of IGF - I and small airway wall thickness （r = 0772, P 〈 0.01 ） . The negative correlation was observed between the expression of IGF - I and FEV0.3/FVC（% ） （r = - 0.511, P 〈 0.01）. Conclusion Chronic exposure to cigarette smoking and intratracheal administration of poreinepancreatic elastase （PPE） can result in COPD in experimental rats. Airway remodeling was founded in small airway of COPD rat model, IGF - I may play an important role in the airway remodeling of COPD.