氯沙坦对大鼠肺纤维化的干预作用及机制探讨

Effects of losartan,an angiotensin Ⅱ type 1 receptor antagonist,on experimental pulmonary fibrosis in rats

目的研究AT1受体拮抗剂氯沙坦对博来霉素诱导的大鼠肺纤维化模型的干预作用,并探讨其机制。方法雄性SD大鼠45只随机分为三组,每组15只,分别为对照组、博来霉素组(气管内注入博来霉素)及氯沙坦组(气管内注入博来霉素,并给予氯沙坦灌胃)。采用HE染色了解肺泡炎和肺纤维化的情况,免疫组化检测肺内气道的Ⅰ型胶原,ELISA检测支气管肺泡灌洗液(BALF)中白细胞介素-8(IL-8)和转化生长因子-β1(TGF-β1)水平的变化,并观察BALF中的中性粒细胞数变化。结果氯沙坦组与博来霉素组比较,灌注后第7和21d肺泡炎明显减轻;第21d肺纤维化明显减轻(P均<0·05)。博来霉素组肺间质中Ⅰ型胶原表达持续增强,氯沙坦组Ⅰ型胶原表达明显减少(P<0·05)。氯沙坦组BALF中的中性粒细胞数、IL-8及TGF-β1水平于第7d明显低于博来霉素组(P<0·05),第21d差异无统计学意义(P>0·05)。结论氯沙坦对博来霉素诱导的大鼠肺纤维化模型有抑制作用,其机制可能与抑制TGF-β1水平有关。

Objective To investigate the effects of losartan on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. Methods Forty-five male SD rats were randomly divided into three groups （n = 15 in each group）, ie. bleomycin group（ intratmcheal injected with bleomycin）, losartan group（ intratracheal injected with bleomycin and feed with losartan via a gastric tube）, and control group. The rats were sacrificed 7, 14 and 21 days after the treatment. Lung weights were measured and lung tissues were observed by haematoxylin and eosin stain. The expression of type I collagen in the lung was examined by immunohistochemistry, The levels of interleukin-8（IL-8） and transforming growth factor-β1 （TGF-β1） in bronchoalveolar lavage fluid（BALF） were assayed by enzyme-linked immunosorbent analysis. Neutrophils in BALF were also counted. Results The expression of type Ⅰ collagen in lung was reduced and the increase of neutrophils in BALF was significantly inhibited by losartan. Overexpression of TGF-β1 in BALF on day 7 induced by bleomycin was also suppressed significantly by losartan. Conclusions The pulmonary fibrosis induced by bleomycin could be inhibited by losartan to some extent. The inhibitory effect of losartan may be ascribed to the reduction of TGF-β1 partly.