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作 者:华晓萍[1] 傅大莉[2] 张莉[1] 谭正怀[1]
机构地区:[1]四川省中医药科学院,成都610041 [2]成都军区总医院临床药学科,成都610083
出 处:《中药药理与临床》2016年第3期113-117,共5页Pharmacology and Clinics of Chinese Materia Medica
基 金:四川省科学技术厅成果转化基金项目(11010119)
摘 要:目的:评价肝宝胶囊对2,4-二甲基亚硝胺(DMN)诱导大鼠肝纤维化模型的治疗作用,为临床应用提供依据。方法:雄性SD大鼠腹腔注射DMN 10μl/kg、连续3天/周、持续4周制备大鼠肝纤维化模型后,将动物随机分组,并分别灌胃肝宝胶囊2.0、4.0、8.0g原生药/kg及双环醇0.2g/kg,每天1次,连续4周,末次给药后24小时并禁食不禁水16小时后检测大鼠肝门静脉压、肝重及肝脏/体比、血液生化指标、肝内羟脯氨酸(Hyp)含量、肝内胶原容积百分比、肝内α-平滑肌肌动蛋白(α-SMA)表达及肝组织形态变化。结果:大鼠给予DMN造模4周停药4周后,其肝脏重量及脏/体比、血清总蛋白(TP)、白蛋白(ALB)明显降低,肝门静脉压、血清谷草转氨酶(ALT)、谷丙转氨酶(AST)、碱性磷酸酶(ALP)及肝内Hyp含量、胶原容积百分比、α-SMA表达明显升高,组织学检查肝脏纤维化严重;肝宝胶囊2.0g生药/kg可显著降低肝门静脉压、肝内Hyp含量、胶原容积百分比、α-SMA表达以及肝纤维化级别;肝宝胶囊4.0g生药/kg可显著增加肝脏/体比,显著降低α-SMA表达以及肝纤维化级别;肝宝胶囊8.0g生药/kg可显著增加肝脏/体比,显著降低肝内Hyp含量、胶原容积百分比、α-SMA表达以及肝纤维化级别。结论:肝宝胶囊对DMN诱导的大鼠肝纤维化有较好的治疗效果,这些作用可能与其能够抑制肝星状细胞活化有关,其作用机理有待进一步探讨。Objective: To evaluate the therapeutic effect of Ganbao capsule on hepatic fibrosis, providing experimental data for its clinical applica- tions. Methods: Liver fibrosis were induced by intraperitoneal injection of dimethylnitrosamine (DMN) ( 10μl/kg, 3d/week) for 4 weeks in male rats. Then these rats were divided into 5 groups, and were intragastric administration of Ganbao capsule groups (2.0g/kg, 4.0g/kg, 8. 0g/kg) ,bicyclol group (0.2g/kg) and model groups respectively, once a day for 4 weeks. On the 57th day, the rats were anesthesia to measure the hepatic portal venous pressure, the blood were taken to measure the activities of ALT, AST and ALP, the levels of TP and ALB. Then the rats were killed and the liver were weighted and checked the contents of Hyp, expressions of α-SMA and pathology. Results: Intra- peritoneal injection of DMN significantly decreased the absolute weight and index of liver, the levels of TP and ALB in serum; increased the pressure of hepatic portal venous, the activities of ALT, AST and ALP in serum, the content of Hyp and the expression of α-SMA in livers. Under the microscope, the liver become severely fibrosis in rats. Ganbao capsule 2.0g/kg significantly decreased the hepatic portal venous pressure, content of Hyp, expression of α-SMA and the degrees of the liver fibrosis in DMN-treated rats. Ganbao capsule 4.0g/kg signifi- candy increased liver index but decreased the content of Hyp and expression of α-SMA in lever and improved the liver fibrosis in DMN-treated rats While Ganbao capsule 8.0g/kg markedly increased the liver index; reduced the content of Hyp and expression of α-SMA in liver, and and improved the liver fibrosis in DMN-treated rats. Conclusion: Ganbao capsule has a positively therapeutic effect on hepatic fibrosis in- duced by DMN in rats and the therapeutic mechanism needs to be studied further.
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