氨溴索对实验性肺纤维化的干预作用

Effect of Ambroxol Treatment on Experimental Pulmonary Fibrosis in Rats

目的:探讨氨溴索对博莱霉素所致大鼠肺间质纤维化的干预作用及机制.方法:健康雌性SD大鼠45只,随机分为3组.治疗组:15只,气管内一次性注入博莱霉素5 mg*kg-1,当日予氨溴索20 mg*kg-1灌胃,每日一次,于第7,14和28 d各处死5只;模型组:15只,以生理盐水代替氨溴索灌胃,余同治疗组;对照组:15只,大鼠气管内注入生理盐水0.2～0.3 ml,于第7,14和28 d各处死5只.各组动物处死后提取肺组织,作HE染色,进行病理分析,并测定肺匀浆中谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和羟脯氨酸(HYP)的含量.结果:对照组无明显病理改变;治疗组7 d时肺泡炎较模型组减轻,28 d时纤维化病变较模型组好转.模型组7 d肺匀浆中GSH含量和14 d SOD含量低于对照组(P<0.01),治疗组上述指标较模型组升高(P<0.05, P<0.01).模型组28 d时肺匀浆HYP含量均明显高于对照组和治疗组(P<0.05).结论: 氨溴索能通过增强肺局部抗氧化能力,减轻博莱霉素诱导的肺泡炎和肺纤维化程度,是治疗肺纤维化的可能途径之一.

Objective: To evaluate the effects and mechanism of ambroxol treatment on bleomycin-induced pulmonary fibrosis of rats. Methods: 45 healthy SD rats were randomly divided into three groups. In ambroxol-treated group (n=15), ambroxol was given everyday at a dose of 20 mg·kg -1 after a single intratracheal instillation of bleomycin at a dose of 5 mg·kg -1 . And in each group, 5 animals were killed on day 7, 14 and 28 after instillation respectively. Bleomycin-induced pulmonary fibrosis model group (n=15) were treated with saline instead of ambroxol after instillation of bleomycin. Rats in control group (n=15) were instilled with saline intractracheally. The lungs were harvested for histopathological examination by light microscopy. The contents of GSH, SOD and HYP in the homogenate of the rat lungs were assayed. Results: Amelioration of alveolitis and lung fibrosis after treatment with ambroxol was shown in pathological section. The levels of GSH on day 7 and SOD on day 14 were decreased in model group than in control group (P<0.01, both) and in treated group (P<0.05, P<0.01, respectively). The content of HYP in homogenate was significantly lower in treated group than in bleomycin model group on day 28. Conclusion: Ambroxol could reduce the degree of alveolitis and fibrosis induced by bleomycin through its enhancement of anti-oxidant defence. It suggests that ambroxol should be a new therapeutic way for pulmonary fibrosis.