白三烯抑制剂对博莱霉素所致大鼠肺纤维化的干预作用

目的 观察白三烯抑制剂(LT-S)齐留通对博莱霉素(BLM)所致大鼠肺纤维化模型肺纤维化形成过程的影响.方法 54只SD雄性大鼠随机分为正常组(C组)、模型对照组(M组)和LT-S组(S组)3组,每组18只.S组于气管内滴注BLM(5 mg/kg)诱导肺纤维化,于造模当天开始每日给予齐留通100 mg/kg灌胃;M组以生理盐水代替齐留通灌胃;C组均用生理盐水代替BLM和齐留通.各组动物均于制模后的第7天、第14天和第28天分别随机处死6只动物,分取肺组织行病理切片苏木精-伊红染色和Masson染色观察肺泡炎和肺纤维化程度、碱水解法检测肺组织羟脯氨酸(Hyp)浓度、免疫组织化学技术检测肺组织α平滑肌肌动蛋白(α-SMA)和转化生长因子β1(TGF-β1)水平.结果 S组肺泡炎和肺纤维化程度及肺组织Hyp含量均显著低于M组,其TGF-β1和α-SMA在肺组织中的表达水平亦均显著低于M组.结论 LT-S可减轻BLM诱导的大鼠肺纤维化,并可能通过抑制TGF-β1蛋白表达而实现对成纤维原细胞增殖的抑制.

Study of leukotrienes inhibitor on bleomycin-induced pulmonary fibrosis in rats

Objective To investigate the effect of zileuton, leukotrienes inhibitor, on pulmonary fibrosis induced by bleomycin(BLM) in the rats. Methods Fifty-four adult male Sprague-Dawley rats were divided randomly into three groups: BLM group (M group), control group (C group) and leukotriene inhibitor group(S group). Each group contained eighteen mice. S group was treated with zileuton everyday at a dose of 100 mg/kg after a single intratracheal instillation of BLM at a dose of 5 mg/kg; M group was treated with saline instead of zileuton after instillation of bleomyein;C group was treated with saline instead of zileuton and BLM. Six rats in each group were killed on 7,14 and 28 days after instillation. The rat lungs were harvested for HE and Masson trichrome stain, hydroxyproline content was determined, immunohistochemistry was used to detect the expressions of α-SMA and TGF-β1 in the lung tissues. Results The hydroxyproline content of M group was significantly higher than that of S group, the degree of alveolitis in S group was ameliorated as compared with that in M group(P＜0.05);a significantly reduced fibrosis was observed in S group compared with that in M group. The expression of TGF-β1 and α-SMA in lung tissue of S group was significantly lower than that of M group. Conclusions Leukotriene inhibitor could reduce the degree of bleomycin-induced pulmonary fibrosis in rats. It may inhibite the proliferation of fibroblasts by inhibiting the expresson of TGF-β1 in lung tissue.