血管内皮生长因子与慢性支气管炎合并肺气肿大鼠早期肺动脉重构关系的研究

Association between vascular endothelial growth factor and early remodeling of pulmonary arteries of chronic bronchitis with emphysema in rats

目的研究血管内皮生长因子（VEGF）在慢性支气管炎合并肺气肿早期（非低氧血症期）肺动脉重构中的作用及N-乙酰半胱氨酸（NAC）的抗氧化作用对其的影响。方法24只健康雄性Wistar大鼠随机分为4组，每组6只：假吸烟组（A组）、慢性支气管炎合并肺气肿组（B组）、NAC预防组（C组）、NAC治疗组（D组），B、C及D组采用两次气管内注入脂多糖（LPS）及烟熏4周法制备慢性支气管炎合并肺气肿大鼠模型，C组在烟熏及气管内注入LPS前每天给予NAC（50mg／只）灌胃，D组在第15～28天烟熏前每天给子NAC（50mg／只）灌胃。各组作血气分析、对肺组织进行苏木精-伊红染色、维多利亚蓝＋VG（Van—Gieson）染色观察气道炎症、肺泡面积改变、肺血管改变及采用免疫组化法观察VEGF的表达情况。结果与A组比较，B组各大鼠小气道出现组织细胞损伤、管壁炎症细胞浸润及平均肺泡面积增大（P〈0.05），符合慢性支气管炎合并肺气肿的病理改变；B组动脉氧分压、氧饱和度及二氧化碳均在正常范围。与A组比较，B组肺血管管壁增厚、管腔缩小（P〈0．01），且肌化动脉、部分肌化动脉比率增加（P〈0．01），VEGF在肺动脉周围表达增多（P〈0.01）。而C组及D组经NAC抗氧化干预后肺血管管壁增厚及管腔缩小减轻（P〈0．05），并且肌化动脉、部分肌化动脉比率减少（P〈0．01），肺动脉周围VEGF表达比B组减少（P〈0．01）。结论由吸烟及LPS诱导的大鼠慢性支气管炎合并肺气肿早期（非低氧皿症期）VEGF表达增多参与了肺动脉重构，NAC可抑制肺动脉重构与其通过抗氧化作用降低VEGF表达有关。

Objective To investigate the role of vascular endothelial growth factor（VEGF） in rat remodeling of pulmonary arteries of chronic bronchitis （CB） with emphysema in early stage （normoxic period） ,and the antioxidant effect of NAC on these changes. Methods Twenty-four health Wistar rats were remdomly divided into four groups： Sham group （group A）, CB with emphysema group （group B）, NAC prevention group（group C） and NAC treatment group（group D）. Group B, group C and group D were instilled intratracheally with LPS twice and exposed to cigarette smoking for four weeks to induce CB with emphysema model. Group C was administrated with NAC 50 mg a rat before LPS and smoking. Group D was administrated with NAC 50 mg a rat from 15-28 days before smoking during the model producing period. Blood gas analysis of each rat had been made. The morphology changes of small airways, areas of alveoli, pulmonary arteries and the expression of VEGF had been observed by the method of immunohistochemistry. Results Compared with those of group A, the small airways in group B showed that the tissues and cells were injured and the inflammatory cells infiltrated the airway walls, and the average areas of alveolus increased（ P 〈0.05）. In other hand, PaO2, SaO2 and PaCO2 in group B were all in the normal range. Compared with those of group A , the vessel walls of pulmonary arteries had been showed thickening （ P 〈0.01） ,and the ratio of muscular arteries and partial muscular arteries increased（ P 〈0.01）,and with the expression of VEGF around pulmonary arteries in group B increased（ P〈0.01）. But group C and group D with the treatment of NAC compared to group B,the thickening of the vessel walls had been reduced（ P 〈 0.05）, and the ratio of muscular arteries and partial muscular arteries decreased （P 〈 0.01）, and the expression around the pulmonary arteries decreased （P 〈 0.01）. Conclusions VEGF involved in the remodeling of pulmonary arteries in CB with emphysema in rat induced by cigarette smoking and LPS in early stage （normoxie period） ,and the antioxidant of NAC can inhibite the remodeling of pulmonary arteries associated through decreasing the expression of VEGF.