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目的本实验采用BLM诱导的大鼠肺纤维化模型,研究LEF对博莱霉素诱导的大鼠肺纤维化模型的影响作用,并与其他治疗类风湿性关节炎的药物进行比较。方法首先采用BLM制备大鼠肺纤维化模型,1次/d,经口灌胃给予LEF和地塞米松(Dexamethasone,DEX),同时设CMC溶剂对照组,连续给药4周。分别于给药后1、2和4周解剖大鼠,采集出肺血液,检测MDA和NO2-/NO3-的含量;采集肺组织,制备切片,分别采用HE、Masson三重染色和天狼猩红染色方法检查大鼠肺组织出现肺炎和肺纤维化的病理变化程度,采用组织芯片技术结合免疫组织化学方法检查TGF-β1在肺组织中不同部位的表达情况。结果在给药后1、2和4周,与CMC组相比,LEF、DEX组大鼠出现肺血液中MDA和NO2-/NO3-的含量明显降低,LEF、DEX组大鼠出现肺炎和肺纤维化程度明显降低;与CMC组相比,LEF、DEX组大鼠肺组织中TGF-β1表达阳性程度明显降低。结论研究结果提示,国内生产的来氟米特对博莱霉素诱导的大鼠肺纤维化模型的早期炎症反应具有一定抑制作用。
OBJECTIVE: To investigate the effect of LEF on bleomycin-induced rat pulmonary fibrosis model by using BLM-induced rat pulmonary fibrosis model and to compare with other drugs for the treatment of rheumatoid arthritis. Methods Pulmonary fibrosis model was established by BLM. LEF and Dexamethasone (DEX) were orally administrated by oral gavage once a day for 4 weeks. Rats were dissected at 1, 2, and 4 weeks after the administration, lung blood was collected and MDA and NO2- / NO3- contents were detected. Lung tissues were harvested and sections were prepared for HE staining, Masson’s triple staining and Sirius red staining Methods The pathological changes of lung and pulmonary fibrosis were observed in rats. The expression of TGF-β1 in different parts of lung tissue was examined by tissue microarray and immunohistochemistry. Results Compared with CMC group, the levels of MDA and NO2- / NO3- in lungs of rats in LEF and DEX groups were significantly decreased at 1, 2 and 4 weeks after administration, while pneumonia and lungs were found in LEF and DEX groups Compared with CMC group, the expression of TGF-β1 in lung tissue of LEF and DEX groups was significantly lower than that of CMC group. Conclusions The results suggest that domestic production of leflunomide may have an inhibitory effect on the early inflammatory response induced by bleomycin-induced pulmonary fibrosis in rats.