熊果酸抗实验性大鼠肝纤维化作用机制的研究

目的观察熊果酸对实验性大鼠肝纤维化的影响及可能的作用机理。方法将不同剂量的熊果酸10mg(kg/d)、20mg(kg/d)、40mg(kg/d)作用于二甲基亚硝胺(DMN)所致肝纤维化大鼠,在药物治疗4周后观察熊果酸对肝纤维化大鼠肝功能的影响;观察熊果酸对氧化指标SOD、MDA的影响;病理学方法观察熊果酸治疗后组织形态学的变化;RT-PCR方法检测熊果酸对MMP-1mRNA、TIMP-1mRNA表达变化。结果熊果酸可明显改善肝纤维化大鼠肝功能,并呈剂量依赖性;不同剂量熊果酸作用4周后能显著增加SOD表达,降低MDA表达;在病理学形态方面,熊果酸治疗组使肝组织结构不同程度改善;不同剂量熊果酸作用4周后RT-PCR方法检测治疗组MMP-1mRNA的表达较模型组相比明显升高,TIMP-1mRNA表达较模型组相比显著降低。结论熊果酸可明显改善肝纤维化大鼠肝功能,并呈剂量依赖性;熊果酸能显著增加SOD表达,降低MDA表达;熊果酸可上调MMP-1mRNA的表达,下调TIMP-1mRNA的表达;熊果酸治疗肝纤维化的作用机制可能与阻断氧化应激过程,抑制脂质过氧化,增加细胞外基质(ECM)的降解,减少ECM的沉积等机制有关。

Effect of Ursolic acid on a rat liver fibrosis model

Objective To observe the effect of Ursolic acid on a rat liver fibrosis model and possible mechanisms.Methods Given Ursolic acid to DMN induced liver fibrosis rat by intraperitoneal injection at the dose of 10mg/kg,20mg/kg,40mg/kg once per day for successive 4 weeks.At the end of this experiments, the effect of Ursolic acid on the liver function and oxidation indexes was observed by measuring the indexes of ALT,AST,TP,ALB,A/G and SOD,MDA in serum.The morphological change of liver tissue was observed under the light microscope via the HE dyeing.The changes of MMP-1mRNA and TIMP-1mRNA expression levels induced by Ursolic acid were measured using RT-PCR.Results Ursolic acid could significantly improve liver function in dose-dependent manner compared with the model group and colchicine group. Different concentrations of Ursolic acid for 4 weeks, Ursolic acid could significantly increase the expression of SOD,whereas decrease the expression of MDA. MMP-1mRNA expression levels induced by Ursolic acid were significantly higher than that of model group and colchicine group,but TIMP-1mRNA expression levels significantly lower.Conclusion Ursolic acid could significantly improve liver function in dose-dependent manner; Ursolic acid could significantly increase the expression of SOD and decrease the expression of MDA.Ursolic acid could up-regulate MMP-1mRNA expression levels and down-regulate TIMP-1mRNA expression levels;Our results suggested that the possible mechanisms of Improvements of liver fibrosis induced by Ursolic acid were associated with blocking oxidative stress,inhibiting lipid peroxidation,increasing ECM degradation and decreasing ECM deposition.