【摘要 】 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% BLMA₅ 0.1 ml/100 g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. 10 μg/100 g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。

Jiang Li, Chen Baiyi, Li Zhenhua, et al. Institute of Respiratory Disease, China Medical University. Shenyang110001

【Abstract 】 Objective It has well been known that cytokines and extracellular matrixprotein (ECM) have played an important role in pulmonary fibrosis in animal model as wellas in patients. The purpose of this study was to evaluate the suppressive effect ofcolchicine (Colc.) in bleomycin (BLM)-treated rats. Method Consecutive changes of interleukin-6(IL-6) andinterleukin-8 (IL-8) released by alveolar macrophage (AM) were measured with murine B-cellhybridoma 7TD1 cells and micro membrane filter test. ECM and lipid peroxidation wereobserved with radioimmunoassay and biochemical assay respectively. Result (1) Colc. significantly suppressed release of IL-6 by AMfrom day 7 to 28 (P<0.05). But the level of IL-6 remained higher than that of thecontrol. On the day 1 to 3, IL-8 released by AM markedly decreased (P<0.01) and thepeak of IL-8 secretion had not appeared. (2) Colc. had no protective effects on AM lipidperoxidation injury. (3) Colc. markedly decreased the level of fibronectin (FN) by AM onday 7, 14 (P<0.01), as well as the level of laminin (LN) in bronchoalveolar lavagefluid (BALF) on day 7 to 28. However, the level of LN remained higher than that ofcontrol. (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 thedegree of fibrosis in the late stage. Conclusion Lipid peroxidation of AM might be one of the mechanisms of tissueinjury and of AM activation, which increases the release of cytokines (IL-6, IL-8) anddeposition of extracellular matrix proteins (FN, LN). Colc. exertes somewhat inhibitoryeffects on the process of pulmonary fibrosis in animal model. Factors other than AM andits cytokines might also be involved in the pathogenesis of pulmonary fibrosis inexperimental rats.

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