芍药苷对大鼠放射性肝纤维化的保护作用和机制研究

目的探讨芍药苷对大鼠放射性肝纤维化的保护作用及机制。方法建立雄性SD大鼠放射性肝纤维化实验动物模型,将大鼠随机分为正常对照组、模型组、芍药苷治疗组(20、40、80 mg·kg-1),每组10只。除正常对照组外,其余各组均制备成放射性肝纤维化模型,造模后各组每天给予相应药物灌胃。于照射后第26周末处死大鼠,检测大鼠血清中AST、ALT的活性,ELISA法测血清中TGF-β1、HA、PC-Ⅲ、LN含量;光镜下观察肝脏HE染色、MASSON染色病理改变;碱水法检测大鼠肝脏组织中羟脯氨酸(Hyp)含量,免疫组化法测肝脏组织TGF-β1、Smad3/4/7蛋白表达情况。结果与正常对照组比较,模型组大鼠肝脏损伤和胶原纤维增生明显,其血清中AST、ALT活性明显升高,血清中TGF-β1、HA、PC-Ⅲ、LN含量明显增加,大鼠肝脏组织中Hyp含量增加,另外大鼠肝脏组织中TGF-β1、Smad3/4/7蛋白表达增加。与模型组比较,芍药苷治疗组可明显抑制大鼠血清中AST、ALT活性的升高,降低血清中TGF-β1、HA、PC-Ⅲ、LN的含量,降低肝脏组织中Hyp含量,减轻肝脏损伤程度及胶原纤维增生程度;芍药苷治疗组可减少大鼠肝脏组织中TGF-β1和Smad3/4/7蛋白表达。结论芍药苷具有明显的抗肝纤维化作用,其机制可能与其阻断TGF-β1/Smad信号传导通路有关。

Effect of Paeoniflorin on TGF-β/smad Signal Transduction Pathway in Rats with Radioaction-induced Hepatic Fibrosis

Objective To investigate the protective effect of paeoniflorin on radiation-induced hepatic fibrosis in rats and its mechanism.Methods Fifty healthy male Sprague-Dawley rats were randomly assigned to normal control group,model group,and paeoniflorin treatment groups(20,40,80 mg · kg-1).Each group contained 10 rats.Each group,except the normal control group,received X-ray exposure to establish radiation-induced hepatic fibrosis model rats.All the rats were administered with corresponding drugs.Rats were sacrificed by cervical dislocation 26 weeks after irradiation.The blood and liver of the rats were collected for further examinations.The level of hydroxyproline(Hyp) in liver tissues and serum activities of ALT and AST were detected.The serum level of TGF-β1,HA,PC-Ⅲ and LN was measured.Histology was observed with hematoxylin-eosin staining and Masson′s trichrome staining by optical microscopy.Meanwhile,the expression of TGF-β1,Smad3/4 and Smad7 proteins was detected by immunohistochemistry.Results Radiation-induced liver damage and collagen deposition in the model group were more severe than in the normal control group.The activities of ALT,AST and TGF-β1,HA,PC-Ⅲ,LN and the liver Hyp contents were significantly higher in the model group than in the normal control group.The