复方肝毒清影响二甲基亚硝胺诱导大鼠肝纤维化的机制研究

Effects of Ganduqing on liver fibrosis in rats induced by dimethylnitrosamine

目的探讨复方肝毒清的抗肝纤维化机制。方法以二甲基亚硝胺(DMN)制备大鼠肝纤维化模型,分别以去铁铵腹腔注射及高、低剂量复方肝毒清灌胃给药。观察去铁铵和复方肝毒清对大鼠肝功能、血清铁及肝组织病理学和转化生长因子-β1(TGF-β1)m RNA表达的影响。结果去铁铵与高、低剂量中药复方均能明显降低血清丙氨酸氨基转移酶(ALT)水平及肝组织TGF-β1m RNA表达,与模型组比较,差异有统计学意义(均P<0.01)。在模型组,伴随着肝星状细胞(HSC)大量活化,大鼠铁负载显著增加;铁沿纤维间隔分布,而且铁主要沉积于库普弗细胞和HSC。去铁铵及复方肝毒清能使肝组织铁负载明显减轻,胶原纤维沉积和肝细胞变性坏死明显改善。结论复方肝毒清的抗肝纤维化机制与其调节体内铁的代谢和转运及进一步抑制HSC活化有关。

Objective To investigate the anti-fibrosis mechanism of Ganduqing. Methods Rat model of hepatic necrosis and subsequent fibrosis was induced by dimethylnitrosamine（DMN）. Rats were respectively administrated with desferrioxamine and Ganduqing decoction. The liver function and serum level of iron were detected. Histopathology of liver tissues and the expression of transforming growth factor- β1（TGF-β1） m RNA were examined. Results The serum level of alanine aminotransferase（ALT）and TGF-β1m RNA expression of liver tissues in desferrioxamine group,Ganduqing high-dose and low-dose groups were obviously decreased. Compared with the control group, there were statistical significant differences（all P 〈0.01）. In control group, accompanied with the activation of hepatic stellate cells（HSCs）, iron not only distributed in fibrous septa, but also mainly deposited in kupffer cells（KCs） and HSCs.Desferrioxamine and Ganduqing therapy reduced the iron load in liver tissue, and significantly improved collagen deposition, hepatocytes denaturation and necrosis. Conclusion The anti-fibrosis mechanisms of Ganduqing may be related to the regulatory action on iron metabolism and transport in liver tissues, which suppresses the activation of HSC.