海洋小分子XF-1抗肺纤维化的实验研究

Anti-fibrotic effect and mechanisms of the marine derived XF-1 on pulmonary fibrosis in rats

目的探讨海洋来源小分子XF-1对博莱霉素(BLM)诱导肺纤维化模型大鼠的治疗作用。方法首先通过建立TGF-β诱导肺上皮细胞模型,观察不同浓度XF-1的抑制效果。然后采用气道滴注BLM溶液构建肺纤维化大鼠模型,通过血象分析仪检测大鼠肺泡灌洗液(BALF)5种炎症细胞的数量,利用酶联免疫吸附法(ELISA)检测BALF上清细胞因子和肺组织羟脯氨酸(HYP)、胶原蛋白含量,通过H&E染色和免疫组化IHC对XF-1改善大鼠肺纤维化的药物效果进行系统评价。结果结果显示XF-1能够有效抑制TGF-β诱导肺上皮细胞的增殖,而且具有毒性低的优点。XF-1还可显著改善肺纤维化大鼠体质量降低的状况,有效降低大鼠BALF中的TGF-β1、TNF-α和MCP-1等炎症细胞因子的含量,抑制肺组织HYP、胶原蛋白的表达水平,显著抑制α-SMA的组织表达,这表明XF-1能够明显改善大鼠肺组织炎症浸润、纤维化以及胶原沉积,可作为抗肺纤维化的候选化合物用于进一步研究。

Objective To investigate the therapeutic effect of XF-1 on bleomycin-induced pulmonary fibrosis in rats.Methods Firstly,the animal model of pulmonary fibrosis was established by instilling BLM solution into the rat airway,then the 5 kinds of lymphocytes number in bronchoalveolar lavage fluid(BALF)of rats were counted by hemogram analyzer.Secondly,inflammatory cytokines in the supernatant of BALF and the hydroxyproline as well as collagen proteins in lung tissue were measured by ELISA.Then the effect of XF-1 on pulmonary fibrosis was evaluated by H&E and Masson staining methods.Results The results showed that XF-1 could significantly improve the lung dysfunction of rats,effectively reduce the contents of inflammatory cytokines such as TGF-β1,TNF-αand MCP-1 in the supernatant of rat alveolar lavage fluid,and dramatically inhibit the levels of hydroxyproline and collagen in lung tissue.The inflammatory infiltration,fibrosis and collagen deposition in rat lung tissue were obviously improved.