多索茶碱对机械通气诱发COPD大鼠肺炎症反应的影响

Effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease

目的评价多索茶碱对机械通气诱发慢性阻塞性肺疾病(COPD)大鼠肺炎症反应的影响。方法清洁级健康成年雄性SD大鼠30只,8周龄,体重200~250 g,采用随机数字表法分为3组(n=10):对照组(C组)、COPD组和多索茶碱组(Dox组)。C组在常氧下饲养2个月,第1和30天气管注射生理盐水0.2 ml;其余组大鼠每天暴露烟雾30 min,持续2个月,第1和30天气管注射LPS 200 μg(0.2 ml)。2个月后各组大鼠麻醉后行气管插管术、机械通气;气管插管后即刻,Dox组静脉注射多索茶碱50 mg/kg;C组和COPD组静脉注射等容量生理盐水。机械通气120 min后取肺组织标本,检测肺组织湿重/干重(W/D)比值和病理学改变;采用ELISA法检测肺组织TNF-α和IL-10含量。结果C组肺组织未见病理改变,其余2组肺组织出现COPD病理学改变;与C组比较,其余各组肺组织W/D比值、TNF-α含量升高,IL-10含量降低(P<0.05)。与COPD组比较,Dox组肺组织W/D比值、TNF-α含量降低,IL-10含量升高(P<0.05)。结论多索茶碱可减轻机械通气诱发COPD大鼠肺炎症反应。

Objective To evaluate the effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease(COPD). Methods Thirty adult male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups(n=10 each)using a random number table method: control group(C group), COPD group and doxofylline group(Dox group). Rats were fed in normoxia for 2 months, and normal saline 0.2 ml was injected into the trachea on 1st and 30th days in C group.Rats were exposed to cigarette smoke for 30 min every day, lasting for 2 months, and lipopolysaccharide 200 μg(0.2 ml) was injected into the trachea on 1st and 30th days in COPD and Dox groups.Two months later, rats in each group were anesthetized, tracheally intubated, and then mechanically ventilated.Doxofylline 50 mg/kg was intravenously injected immediately after intubation in Dox group, and the equal volume of normal saline was given instead in C and COPD groups.Pulmonary specimens were taken after 120 min of mechanical ventilation for examination of pathological changes and for determination of wet/dry weight ratio(W/D ratio) and tumor necrosis factor-alpha(TNF-α) and interleukin-10(IL-10) contents(by enzyme-linked immunosorbent assay). Results No significant pathological change of lung tissues was found in C group, and COPD pathological changes were observed in COPD and Dox groups.Compared with C group, the W/D ratio and TNF-α level were significantly increased, and the IL-10 level was decreased in COPD and Dox groups(P<0.05). Compared with COPD group, the W/D ratio and TNF-α level were significantly decreased, and the IL-10 level was increased in Dox group(P<0.05). Conclusion Doxofylline can reduce the pulmonary inflammatory response induced by mechanical ventilation in rats with COPD.