己酮可可碱可降低实验性阻塞性肺气肿大鼠炎性反应

目的观察己酮可可碱(pentoxifylline,PTX)对实验性阻塞性肺气肿大鼠气道及全身炎性反应变化的影响,及其干预作用。方法采用Wistar大鼠36只,雌雄各半,分为对照组、实验性阻塞性肺气肿模型组(简称模型组:采用被动熏香烟加尾静脉注射内毒素的方法制备阻塞性肺气肿模型)、PTX干预组(模型制备同模型组,从第1天起每天熏烟或在注射内毒素前0.5 h腹腔内注射PTX 15 mg/kg,连续注射30 d)。模型制备后,测定各组肺功能;应用ELISA方法测定血清中肿瘤坏死因子(TNF-α)、白细胞介素-8(IL-8)、IL-10水平,及肺泡灌洗液中IL-6、IL-8含量。病理标本取每只大鼠右下肺叶最大横径气管分叉上组织横纵截面石蜡固定,HE染色光镜观察。结果肺功能:模型组肺功能测定FEV0.2/FVC%显著低于对照组(P<0.01),PTX干预组的FEV0.2/FVC%高于模型组,但低于空白对照组(P均<0.01)。细胞因子:3组间血清IL-8、IL-10、TNF-α差异有统计学意义(P均<0.01)。模型组肺泡灌洗液中IL-6水平高于对照组(P<0.01)。模型组与人类COPD病理变化类似,PTX干预组可见炎性浸润较模型组减少,肺气肿的形成较模型组明显减轻。结论PTX可以减少炎性反应损伤,减轻肺气肿形成,缓解肺功能损伤程度。

Effects of Pentoxifylline on the Inflammatory Reaction in Experimental Obstructive Emphysema Rat Models

Objective Pentoxifylline(PTX) has been shown to suppress the cytokine production. This study aimed to investigate the effects of PTX on the production of proinflammatory cytokines, and correlation between the inflammation and obstructive emphysema in rat models. Methods Thirty-six Wistar rats were randomly divided into 3 groups. ① Normal group(n=12), rats were bred in canonical environment. ② Obstructive emphysema model groupⅠ(n=12), 3 mg/kg lipopolysaccharide was injected intravenously once every two weeks and the rats were exposed to 5% of cigarette smoke,0.5 h/each time, twice daily for 45 days. ③ Model group Ⅱ(n=12), they were the same as those of obstructive emphysema model groupⅠ, but 15 mg/kg pentoxifylline was injected intraperitoneally once daily at the 1 to 30 days. Results The pathologic change of airway and lung tissues of obstructive emphysema models were similar to those of COPD patients. Pulmonary function of the obstructive emphysema model group(FEV0.2/FVC%) were significantly worse than those of normal group and the model groupⅡ(P<0.01). The level of IL-8, IL-10, TNF-α was significantly different from those of the obstructive emphysema model group Ⅰ and model group Ⅱ(P<0.01). Conclusion Experimental obstructive emphysema rat models were successfully established by passive cigarette smoking and injection of lipopolysaccharide. The treatment with PTX could make the pathologic change of airway and lung tissues milder than those of obstructive emphysema model group, and inhibit the production of these proinflammatory cytokines, PTX may reduce damage to the lung in obstructive emphysema.