红芪黄酮对肺纤维化模型大鼠肺组织转化生长因子-β1表达及超微结构的影响

Effects of Hedysari Flavonoids on TGF-β1 and Ultrastructure in Lung Tissue of Rats with Pulmonary Fibrosis

目的观察红芪黄酮对肺间质纤维化模型大鼠转化生长因子-β1(TGF-β1)蛋白表达及肺组织超微结构的影响,并探讨其作用机理。方法 Wistar大鼠随机分为空白组、模型组、强的松组及红芪黄酮高、中、低剂量组,采用气管内滴注博莱霉素方法建立肺纤维化模型,造模后第2日起,各给药组分别给予相应剂量药物,连续灌胃治疗,于第7、14、28日采用免疫组化法检测各组大鼠肺组织TGF-β1的含量表达,透射电镜观察第28日各组大鼠肺组织超微结构变化。结果空白组少数细支气管黏膜上皮细胞胞浆内可见少量TGF-β1蛋白表达;第7、14、28日模型组大鼠支气管、细支气管黏膜上皮细胞TGF-β1表达与空白组比较明显增强(P<0.05),第7、14、28日红芪黄酮高、中剂量组及强的松组与模型组比较,TGF-β1表达均显著减弱(P<0.05,P<0.01)。第28日电镜观察模型组大鼠肺泡纵隔内胶原纤维明显增多,肺泡Ⅱ型细胞胞质线粒体肿胀,线粒体嵴断裂或消失,板层体明显减少;各给药组胶原纤维明显减少,均可改善肺泡Ⅱ型上皮细胞超微结构的异常改变。结论红芪黄酮可明显改善肺纤维化大鼠的病理损伤、减少细胞外基质沉积,可能与抑制TGF-β1表达有关。

Objective To observe the effects of Hedysari flavonoids on TGF-β1 and ultrastructure in lung tissue of rats with pulmonary fibrosis, and explore its mechanism. Methods Wistar rats were randomly divided into blank group, model group, prednisone group and Hedysari flavonoids high-, medium- and low-dose groups. Pulmonary fibrosis model was established by injection of bleomycin via trachea. After 24 h, rats were given drugs by gavage in all treatment groups once daily. The expression of TGF-β1 in lung tissue was detected by immunohistochemistry on d7, d14 and d28, and ultrastructure wasobserved by transmission electron microscope on d28. Results The positive expression of TGF-β1 was found in a few bronchiolar epithelial cell cytoplasm of blank group. Compared with the blank group, the positive expression of TGF-β1 on bronchial epithelial cell significantly increased （P〈0.05） on d7, d14, and d28 in model group. Compared with the model group, the positive expression of TGF-β1 were significantly decreased （P〈0.05, P〈0.01） in Hedysari flavonoids high- and medium-dose groups and prednisone group on d7, d14 and d28. With electron microscopy, collagen fibers within the mediastinum in rat alveolar in model group were significantly increased, cell cytoplasm mitochondria was swollen in type Ⅱ epithelial cell.Mitochondrial crista was broken or disappeared, lamellar bodies significantly reduced. Collagen fibers reduced significantly in all treatment groups, which can improve and change ultrastructure on type Ⅱ epithelial cell. Conclusion Hedysari flavonoids can significantly reduce pathological damage and extracellular matrix deposition of rats with pulmonary fibrosis, which may have connection with inhibiting of TGF-β1 expression.