目的:研究昆布提取物J201对大鼠肺纤维化的治疗作用及其可能的作用机制。方法:Wistar大鼠64只,随机分为4组。气管内灌注博莱霉素(BLM)诱导肺纤维化模型,观察BLM诱导的大鼠肺纤维化经不同剂量的J201治疗后,肺组织形态学、肺系数、丙二醛(MDA)和羟脯氨酸(HYP)含量的变化以及Fas、Fas配体(FasL)、基质金属蛋白酶-9(MMP-9)、组织金属蛋白酶抑制剂-2(TIMP-2)表达的变化。结果:J201能明显改善BLM诱导的大鼠肺纤维化肺组织形态学改变,并呈现一定的量效关系;能显著降低肺系数、肺组织MDA和HYP的含量,对肺组织Fas、FasL、MMP-9、TIMP-2的表达有明显的抑制作用,对肺系数、MDA、HYP、Fas、FasL、MMP-9 TIMP-2的影响呈现一定的量效关系。结论:J201对实验性大鼠肺纤维化有一定的保护作用,抗氧化作用及抑制Fas、FasL、MMP-9、TIMP-2的表达是其可能的机制之一。
AIM: To investigate the protective effect of Okam extract J201 on bleomycin induced pulmonary fibrosis in rats and the underlying mechanism. METHODS: Forty-six Wistar rats were randomly divided into four groups. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin. The histopathological changes of the lungs, lung weight index, contents of malondialdehyde (MDA) and hydroxyproline ( HYP ) in lung homogenate were investigated, and the immunohistochemical techniques were used to investigate the expressions of factor associated suicide (Fas), Fas ligand (FasL), matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-2 (TIMP-2) with a view to evaluating the effects of J201. RESULTS: Dose-dependent improvement in lung histopathology induced by bleomycin was noted in J201-treated group. Lung weight index and the contents of MDA and HYP were reduced by addition of J201. There were also decreased expressions of Fas, FasL, MMP-9 and TIMP-2 by J201. Dose-dependent relationship was observed, and the expressions of Fas. FasL, MMP-9 and TIMP-2 of pulmonary fibrosis induced by bleomycin were inhibited in rats. The effect of J201 on lung index, MDA, HYP, Fas, FasL, MMP-9 and TIMP- 2 was in a dose-dependent manner. CONCLUSION: J201 shows protective effects on the pulmonary fibrosis induced by bleomycin in rats. Antioxidation and inhibition of the expression of Fas, FasL, MMP-9 and TIMP-2 in lung tissues may be one of the underlying mechanisms.