摘要
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。
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,MG 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-lmRNA and TIMP-lmRNA 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 in- crease the expression of SOD,whereas decrease the expression of MDA. MMP-lmRNA expression levels induced by Ursolic acid were significantly higher than that of model group and colchicine group,but TIMP-lmRNA expression levels significantly lower.Con- clusion 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 aci^t could up-regnlate MMP-lmRNA expression levels and down- regulate TIMP-lmRNA 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.
出处
《江西医药》
CAS
2008年第5期414-417,410,共5页
Jiangxi Medical Journal
