氨茶碱对慢性低氧所致大鼠肺损伤的抑制作用

Inhibitory effects of aminophylline on chronic hypoxic induced lung damage in rats

目的探讨慢性低氧致气道炎症的作用及氨茶碱抑制气道炎症和肺血管损伤的作用。方法成年雄性Wistar大鼠34只,分为对照组(n=10)、低氧组(n=12,每日低氧7h,共21d)、氨茶碱干预组(n=12,每日低氧前灌胃氨茶碱,100mg/kg),用ELISA法检测血清及BALF中TNFα、IL10、IL13含量。取右下肺行HE染色,行定性分析并测量肺小动脉管径。结果低氧组大鼠血清及BALF中TNFα、IL10、IL13含量显著高于对照组(P<0.01),氨茶碱的干预可显著缓解血清及BALF中TNFα的升高(P<0.01),并使血清IL10、BALF中IL10、IL13含量进一步增加(P<0.05,P<0.01和P<0.01);低氧组大鼠FEV0.3/FVC明显低于对照组(P<0.01),与血清TNFα负相关(P<0.01);氨茶碱干预对低氧大鼠肺小动脉壁厚度和面积的增加有减轻趋势。结论慢性低氧可介导气道炎症,氨茶碱对其有拮抗作用并有改善肺血管重塑的趋势。

Objective To investigate the effects of chronic hypoxia and the inhibitory effects of aminophylline on the airway inflammation and pulmonary vascular remodeling in rats. Methods Thirty-four male Wistar rats were randomly divided into three groups: Normal control group(n=10); Hypoxia group(n=12,7h exposed to the hypoxia per day); Aminophlline treated group(n=12,treated with aminophylline, 100 mg/kg/day, before exposed to the hypoxia.). The level of tumor necrosis factor (TNF) -α, interlukin (IL) -10 and IL-13 was determined in serum and bronchi alveolar lavage fluid (BALF) by ELISA. The histological examination for qualitative analysis of inflammation of the right low lungs and quantitative analysis of pulmonary artery were performed. Results The results revealed that the level of TNF-α, IL-10 and IL-13 was significantly increased (P<0.01)in serum and BALF in hypoxia group; Comparing to the hypoxia group, the level of TNF-α was significantly decreased (P<0.01), the level of IL-10 in serum and BALF and IL-13 in BALF was significantly increased (P<0.05, P<0.01 and P<0.01)in aminophylline treated group. FEV 0.3/FVC was significantly decreased in hypoxia group (P<0.01), and it was negatively correlated to the level of TNF-α in serum (P<0.01). Meanwhile, the thickness of pulmonary artery walls tended to be increased and the area of pulmonary artery walls tended to be enlarged, but they had no significant difference in aminophylline treated group. Conclusion Chronic hypoxia induces airway inflammation and impairment of pulmonary ventilated function. Aminophylline has anti-inflammatory effects on airway. And it tends to improve the remodeling induced by chronic hypoxia of pulmonary artery.