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目的:观察黄芪多糖对大鼠胆管结扎肝纤维化模型TGF-β1的影响。方法:40只SD雄性大鼠采用随机分为假手术对照组(Sham,n=15)及胆汁淤积性肝纤维化模型对照组(M,n=20)及药物干预组(Y,n=20)。M及Y组采用胆总管结扎(bile duct ligation,BDL)制备胆汁淤积性肝纤维化模型,Sham组仅作胆总管分离,不作胆总管结扎。Y组于术后1周开始经灌胃给予黄芪多糖,1日1次,共4周。所有大鼠均于术后第5周处死取材。统计分析实验过程大鼠死亡率及腹水发生率,观察实验大鼠肝功能、肝组织羟脯氨酸(Hyp)含量及肝组织学;采用Western blot及免疫组化观察实验大鼠肝组织TGF-β1蛋白表达。结果:与Sham组比较,M组大鼠肝功能显著异常,肝组织纤维增生程度、Hyp含量及TGF-β1蛋白表达量均显著增加(P<0.01);与M组比较,Y组大鼠死亡率、腹水发生率显著下降(P<0.05),肝功能显著改善(P<0.01),肝组织纤维增生程度、Hyp含量及及TGF-β1蛋白表达量显著下降(P<0.01)。结论:黄芪多糖可有效地抑制BDL大鼠肝纤维化模型肝组织TGF-β1表达,这可能也是黄芪汤组分干预胆汁淤积性肝纤维化的主要效应机制之一。
Objective: To observe the effect of Astragalus Polysaccharide on TGF-β1 in rat model of biliary ligation of liver fibrosis. Methods: Forty SD male rats were randomly divided into sham operation group (n = 15) and cholestatic liver fibrosis model group (M, n = 20) and drug intervention group ). Group M and group Y were given cholestatic hepatic fibrosis model by bile duct ligation (BDL). Sham group was only for common bile duct separation and not as common bile duct ligation. Group Y received APS by gavage once a week after operation, once a day for 4 weeks. All rats were sacrificed 5 weeks after surgery. The mortality and the incidence of ascites in rats were statistically analyzed. The liver function, Hyp content and liver histology in experimental rats were observed. Western blot and immunohistochemistry were used to observe the expression of TGF- β1 protein expression. Results: Compared with Sham group, the liver function of M group was significantly abnormal, the degree of fibrosis, the content of Hyp, and the expression of TGF-β1 in liver tissue were significantly increased (P <0.01); Compared with M group, (P <0.05), hepatic function (P <0.01), hepatic fibrosis, Hyp content and TGF-β1 protein expression decreased significantly (P <0.01). Conclusion: Astragalus polysaccharide can effectively inhibit the expression of TGF-β1 in hepatic tissue of BDL rat model of liver fibrosis, which may be one of the main effect mechanism of Astragalus membranaceus intervention on cholestatic liver fibrosis.