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目的研究吡非尼酮(PFD)对实验性大鼠的抗肝纤维化作用。方法45只雄性Wistar大鼠随机均分为3组。模型组腹腔注射1%二甲基亚硝胺(DMN)10 mg/(kg.d),每周连续3d,共4周,制作肝纤维化模型;干预组除应用DMN外,同时给予PFD500 mg/(kg.d)灌胃,1次/d,共4周;模型组及正常组以等体积生理盐水灌胃作对照。4周试验结束时进行组织学检查、电镜观察、血清肝纤维化指标、肝功能及转化生长因子-β1(TGF-β1)检测。结果与模型组相比,干预组大鼠体质量下降较少(P<0.05)、肝脾肿大较轻(P<0.05),血清透明质酸、层粘连蛋白和Ⅳ型胶原浓度均明显低于模型组(P<0.05);干预组血清谷丙转氨酶、谷草转氨酶、总胆红素及TGF-β1含量与模型组相比明显降低(P<0.001);MASSON染色显示,干预组肝脏纤维化及炎症反应明显减轻,无明显假小叶;透射电镜观察证实干预组大鼠肝细胞损伤明显减轻,肝窦及Disse腔内胶原纤维沉积明显减少。结论PFD对实验性大鼠肝纤维化模型具有明显的抗肝纤维化作用,其机制可能与抑制TGF-β1的产生有关,PFD有可能用于肝脏疾病的抗纤维化治疗。
Objective To study the anti-hepatic fibrosis effect of pirfenidone (PFD) on experimental rats. Methods Forty-five male Wistar rats were randomly divided into three groups. The model group was intraperitoneally injected with 10% DMN 10 mg / (kg · d) for 3 days every week for 4 weeks to make the model of hepatic fibrosis. In addition to DMN, the intervention group was given DMD 500 mg /(kg.d) gavage, 1 times / d, a total of 4 weeks; model group and normal group with equal volume of normal saline gavage as a control. At the end of 4 weeks, histological examination, electron microscope observation, serum liver fibrosis index, liver function and TGF-β1 were detected. Results Compared with the model group, the body weight of rats in the intervention group decreased less (P <0.05), hepatosplenomegaly was lighter (P <0.05), and the levels of serum hyaluronic acid, laminin and collagen Ⅳ were significantly lower (P <0.001). Compared with the model group, the levels of AST, AST, total bilirubin and TGF-β1 in the intervention group were significantly decreased (P <0.001). The results of MASSON staining showed that the liver fibrosis And inflammatory response were significantly reduced, no obvious false lobules; transmission electron microscopy confirmed the intervention group rats liver cell injury was significantly reduced, sinusoidal and Disse cavity collagen fibers were significantly reduced. Conclusion PFD has obvious anti-hepatic fibrosis effect on experimental rat hepatic fibrosis model. Its mechanism may be related to inhibiting the production of TGF-β1, and PFD may be used to treat liver fibrosis.