肾气丸对DMN大鼠肝纤维化干预作用研究

Intervention Effect of Shenqi Wan on Dimethylnitrosamine-induced Liver Fibrosis in Rats

摘要:

目的: 以二甲基亚硝胺(DMN)大鼠肝纤维化模型为载体,以肾气丸为研究对象,探讨肾气丸对DMN大鼠肝纤维化的干预作用。 方法: 每周前3 d连续ip DMN(10 mg·kg^-1)4周制备大鼠肝纤维化模型。造模2周末DMN处理组大鼠随机分为肾气丸组和模型组(各10只)。第3周的第1 d起,在继续造模的同时,肾气丸组给予成人70 kg体重的10倍量ig(1.029 g·kg^-1),给药2周。4周末处死全部大鼠,留取肝组织样本和血清,观察大鼠肝功能、肝组织羟脯氨酸(Hyp)及肝组织病理变化,实时定量PCR法观察肝组织肝细胞生长因子(HGF)、平滑肌肌动蛋白(α-SMA) mRNA表达变化。 结果: DMN造模4周,引起大鼠肝功能紊乱,与正常组比较,4周模型组大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性及总胆汁酸(TBA)含量显著升高(P<0.01),血清白蛋白(ALB)含量显著下降(P<0.01)。肝组织羟脯氨酸含量显著升高,为正常组的4.58倍(P<0.01),HGF mRNA表达显著下降(P<0.01),α-SMA mRNA水平显著升高(P<0.01)。与模型组比较,肾气丸组大鼠血清ALB含量显著升高,血清ALT,AST活性及TBA含量显著降低。肾气丸显著降低肝组织羟脯氨酸含量(P<0.05),同时显著降低α-SMA mRNA表达(P<0.01),升高HGF mRNA水平(P<0.05)。 结论: 肾气丸对DMN肝纤维化有较好的疗效,为肝病从肾论治提供了实验依据。

Abstract:

Objective:To investigate the intervention effect of Shenqi Wan on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Method: DMN (10 mg·kg^-1) was administrated intraperitoneally to DMN-treated rats for the first three days per week for 4 weeks, at the second weekend, DMN rats were randomly divided into Shenqi Wan group(n=10)and modle group(n=10). At the first day of the third week, both groups continued to receive weekly DMN treatment for another 2 weeks in addition to daily administration of Shenqi Wan. At the end of the experiment, all rats were sacrificed. Liver tissue specimens and serum were remained to observe liver function, liver tissue hydroxyproline (Hyp) and liver histopathological changes of rats, expression changes of liver tissue hepatocyte growth factor (HGF), smooth muscle actin (alpha-SMA) mRNA were observed by real-time quantitative PCR. Result: Liver dysfunction was based on DMN modeling for four weeks, compared with normal group, the serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) activity and total bile acid(TBA) content in the fourth week model group were significantly increased (P<0.01), serum albumin (ALB) were significantly decreased (P<0.01), liver hydroxyproline content was significantly increased 4.58 fold (P<0.01), HGF mRNA expression was decreased significantly (P<0.01), α-SMA mRNA levels were significantly increased (P<0.01). Compared with model group, serum ALB content in Shenqi Wan group was significantly increased, the serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) activity and TBA content were significantly decreased. Shenqi Wan could significantly reduce liver tissue hydroxyproline content (P<0.05). Shenqi Wan could significantly reduce α-SMA mRNA expression (P<0.01), and elevated HGF mRNA level (P<0.05). Conclusion: Shenqi Wan has a good effect for liver fibrosis and provides an experimental basis for liver disease treatment from kidney.