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

• 作 者: 赵桂荣 何冰 李海潮 宿利 李小玲
• 机 构: 北京医科大学第一医院呼吸内科
• 出 处: 北京医科大学学报
• 发表日期: 1999年03期
• 关键词: 肺纤维化模型 博莱霉素 肺泡巨噬细胞 大鼠 成纤维细胞增殖 白细胞介素 受体拮抗剂 抑制作用 药物作用 作用机制

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 mechanism of interleukin1 receptor antagonist (IL1ra) on pulmonary fibrosis induced by bleomycin (BLM) in rats. Methods: MTT method was used to determine the effect of IL1ra before and 1 week after the model rats alveolar macrophages produce tumor necrosis factor α (TNF  α), and the culture supernatant to promote lung fibroblasts Proliferative ability; The expression of TNFα and plateletderived growth factor (PDGF) mRNA in alveolar macrophages were detected by Northern blot. Results: BLM-induced pulmonary fibrosis model 1 week, the alveolar macrophages TNF  α production and the group of cells to promote fibroblast proliferation supernatant activity compared with the normal control group were significantly enhanced, while IL  1ra (10mg · L-1) on the alveolar macrophages TNF @ production and the group of cell supernatant to promote fibroblast proliferation activity was significantly inhibited. BLM induced pulmonary fibrosis model 1 week alveolar macrophages TNF @, PDGFmRNA expression increased compared with the normal control group, while IL  1ra expression had no significant effect. Conclusion: IL  1ra through the alveolar macrophages of TNF  α production and its inhibition of fibroblast proliferation activity, may play an inhibitory role in the model of pulmonary fibrosis?