白细胞介素-1受体拮抗剂对博莱霉素致大鼠肺纤维化模型的影响

Effect of interleukin 1 receptor antagonist on bleomycin induced pulmonary fibrosis of rats

目的：探讨白细胞介素１受体拮抗剂（ｉｎｔｅｒｌｅｕｋｉｎ１ｒｅｃｅｐｔｏｒａｎｔａｇｏｎｉｓｔ，ＩＬ１ｒａ）治疗博莱霉素（ｂｌｅｏｍｙｃｉｎ，ＢＬＭ）致大鼠肺纤维化模型的作用机制。方法：利用ＭＴＴ法测定经ＩＬ１ｒａ作用前、后１周时该模型大鼠肺泡巨噬细胞产生肿瘤坏死因子α（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒα，ＴＮＦα），及其培养上清促肺成纤维细胞增殖能力的变化；利用Ｎｏｒｔｈｅｒｎ杂交测定肺泡巨噬细胞ＴＮＦα、血小板衍化生长因子（ｐｌａｔｅｌｅｔｄｅｒｉｖｅｄｇｒｏｗｔｈｆａｃｔｏｒ，ＰＤＧＦ）ｍＲＮＡ的表达。结果：ＢＬＭ致肺纤维化模型１周时，肺泡巨噬细胞ＴＮＦα的产生及该组细胞上清的促成纤维细胞增殖活性与正常对照组相比均明显增强，而ＩＬ１ｒａ（１０ｍｇ·Ｌ－１）对肺泡巨噬细胞ＴＮＦα的产生及该组细胞上清的促成纤维细胞增殖活性有明显的抑制作用。ＢＬＭ致肺纤维化模型１周时肺泡巨噬细胞ＴＮＦα、ＰＤＧＦｍＲＮＡ的表达较正常对照组增高，而ＩＬ１ｒａ对其表达无明显影响。结论：ＩＬ１ｒａ通过对肺泡巨噬细胞的ＴＮＦα产生及其对成纤维细胞增殖活性的抑制，可能对该模型的肺纤维化起到抑制作用?

Objective:To investigate the therapeutic mechanism of interleukin 1 receptor antagonist (IL 1ra) on bleomycin induced pulmonary fibrosis of rats. Methods: MTT means was adopt to measure the alternations of alveolar macrophages(AMs) derived tumor necrosis factor α(TNF α)of rats and changes of fibroblasts proliferation induced by the conditional media of AMs in the first week after IL 1ra interfered. Northern blot hybridization was used to analyse the expressions of TNF α and platelet derived growth factor(PDGF) mRNA. Results: The production of AMs derived TNF α and the capacity of fibroblasts proliferating of conditional media of AMs were both elevated obviously in fibrosis group on the 7th day, compared with those in the control group. Whereas, the elevations had been inhibited significantly by IL 1ra(10 mg·L -1 ). The expressions of TNF α and PDGF mRNA of AMs of fibrosis group on the 7th day were increased, compared with those of the control group. IL 1ra(10 mg·L -1 ) had no effect on the expressions. Conclusion: IL 1ra may play a role in interrupting pulmonary fibrosis of the model through inhibiting the production of AMs derived TNF α and the capacity of fibroblasts proliferating of AMs.