目的:研究黄芪水提物、黄芪皂苷对博莱霉素(BLM)所致肺纤维化大鼠血Th1/Th2型细胞因子平衡、TNF-α表达的调节作用及对肺上皮细胞超微结构的影响,探讨黄芪阻抑肺纤维化的效应机制。方法:Wistar大鼠随机分为空白组、BLM模型组、地塞米松组、黄芪水提物组、黄芪皂苷组;气管内注入BLM复制大鼠肺纤维化模型,造模后第2天开始药物干预,14天采用酶联免疫吸附法测定血IFN-γ、IL-4、TNF-α的含量,14天、28天观察肺上皮细胞超微结构变化情况。结果:模型组大鼠血IFN-γ含量降低,IL-4、TNF-α的含量升高(均P〈0.05);与模型组比较,黄芪水提物组、黄芪皂苷组、地塞米松组使大鼠血IFN-γ含量明显升高(P〈0.05),IL-4、TNF-α含量明显降低(P〈0.05);黄芪水提物组、黄芪皂苷组与地塞米松组比较,上述指标均无统计学差异(P〉0.05),超微结构观察,模型组肺泡Ⅱ型上皮细胞数量减少,细胞微绒毛稀少,核不规则,核染色质凝集粗块状,板层小体减少空泡样变,线粒体明显肿胀,肺泡间隔成纤维细胞增生明显,胞质内胶原纤维增多;各治疗组均可改善肺泡Ⅱ型上皮细胞超微结构的异常改变。结论:黄芪水提物、黄芪皂苷对肺纤维化大鼠肺泡Ⅱ型上皮细胞超微结构具有保护作用,调节Th1/Th2型细胞因子的平衡及TNF-α含量可能是其阻抑肺纤维化发生的机理之一。
Objective:To observe the effect of Astragalus decoction and Astragalus saponins on the balance of T helper 1/T helper 2 (Th1/Th2) cytokines,seral TNF-α, and the uhrastructure in BLM-induced pulmonary fibrosis rats, in order to explore its underlying mechanisms. Methods:Wistar rats were evenly randomized into normal, model, Astragalus decoction and Astragalus saponins groups, with dexamethasone as the control. Pulmonary fibrosis model was established by injection of Bleomycin(BLM) via trachea (5 mg/kg). After 24 h, the rats were given the drugs by ig in all groups once daily. At the 14 th day and 28 th day,6 rats were killed and the lungs were collected for observing the nltrastructure. Interleukin-4(IL-4), interferon gamma(IFN-γ) and tumor necrosis factor-α(TNF-α) of the sera were detected by enzyme linked immunosorbent assay( ELISA). Results: In comparison with those of normal group, IFN-γ contents were significantly lower, with IL-4 and TNF-α considerably higher in model group (P 〈 0.05). Compared with those of model group, IFN-7 contents were significantly higher( P 〈 0.05), and the level of both IL-4 and TNF-α was significantly lower( P 〈 0.05). No significant differences were found for the above parameters (P 〉 0.05) among the astragalus decoction, astragalus saponins and dexamethasone groups. Changes in uhrastructure of the model group revealed that the numbers of alveolar type Ⅱ epithelial cells decreased and micmvilli on the surface of the cells were rare, and irregular nucli with nuclear chromatin agglutinated. In addition the inner lamellar bodies decreased, with vacuole-like changes. Most mitochondria were exhibited swelling. Fibroblast in alveolar liquid proliferated significantly and the collagen fibers increased. The degree of fibrosis was more mitigative in each treatment groups by microscope and ultrastructure. Conclusion: Astragalus decoction and astragalus saponins have inhibitory effects on the process of pulmonary fibrosis. T