秋水仙碱对大鼠肺纤维化的干预作用

目的研究秋水仙碱（Ｃｏｌｃ．）对博菜霉素（ＢＬＭ）所致大鼠肺纤维化的干预作用，探讨治疗肺间质纤维化的新途径。方法Ｗｉｓｔａｒ大鼠随机分为３组，每组２５只，１组为ＢＬＭ组，气管内注入０．５％ＢＬＭＡ５０．１ｍｌ／１００ｇ体重，复制肺纤维化动物模型，２组为生理盐水对照组，３组为药物干预组，大鼠于ＢＬＭ灌注后每日胃内灌入Ｃｏｌｃ．１０μｇ／１００ｇ体重。三组动物于气管内灌注后第１、３、７、１４、２８天分别随机处死５只，进行支气管肺泡灌洗并收集灌洗液。采用生物活性检测法，测定肺泡巨噬细胞释放细胞因子的变化，细胞外基质蛋白及脂质过氧化损伤的检测，分别采用放免法及生化法。结果秋水仙碱组于灌胃后第７～２８天，白细胞介素６（ＩＬ－６）水平较ＢＬＭ组降低（Ｐ＜０．０５），但仍高于对照组；ＩＬ－８于第１～３天显著下降（Ｐ＜０．０１）；肺内羟脯氨酸（ＨＹＰ）及纤维连结蛋白（ＦＮ）、层粘连蛋白（ＬＮ）含量明显降低。Ｃｏｌｃ．对脂质过氧化损伤未显示出防护作用。结论秋水仙碱对大鼠实验性肺纤维化有一定防护作用

Studies on the role of colchicine in bleomycin induced pulmonary fibrosis in rats

Objective It has well been known that cytokines and extracellular matrix protein (ECM) have played an important role in pulmonary fibrosis in animal model as well as in patients. The purpose of this study was to evaluate the suppressive effect of colchicine (Colc.) in bleomycin (BLM) treated rats. Method Consecutive changes of interleukin 6(IL 6) and interleukin 8 (IL 8) released by alveolar macrophage (AM) were measured with murine B cell hybridoma 7TD1 cells and micro membrane filter test. ECM and lipid peroxidation were observed with radioimmunoassay and biochemical assay respectively. Result (1) Colc. significantly suppressed release of IL 6 by AM from day 7 to 28 ( P <0.05). But the level of IL 6 remained higher than that of the control. On the day 1 to 3, IL 8 released by AM markedly decreased ( P <0.01) and the peak of IL 8 secretion had not appeared. (2) Colc. had no protective effects on AM lipid peroxidation injury. (3) Colc. markedly decreased the level of fibronectin (FN) by AM on day 7, 14 ( P <0.01), as well as the level of laminin (LN) in bronchoalveolar lavage fluid (BALF) on day 7 to 28. However, the level of LN remained higher than that of control. (4) Colc. lessened the collagen deposition, and the lung hydroxyproline (HYP) content decreased on day 7, 14 and 28 ( P < 0.05) compared with that of the control. (5) Colc. decreased exudation of inflammatory cells in the early response, as well as the degree of fibrosis in the late stage. Conclusion Lipid peroxidation of AM might be one of the mechanisms of tissue injury and of AM activation, which increases the release of cytokines (IL 6, IL 8) and deposition of extracellular matrix proteins (FN, LN). Colc. exertes somewhat inhibitory effects on the process of pulmonary fibrosis in animal model. Factors other than AM and its cytokines might also be involved in the pathogenesis of pulmonary fibrosis in experimental rats.