养肝澳平对大鼠肝纤维化的防护作用及机制探讨

Protective effect and mechanism research of Yanggan Auping mixture on hepatic fibrosis in rats

目的:对养肝澳平合剂治疗肝纤维化的作用进行综合评估,探讨养肝澳平合剂对细胞转化生长因子(TGF)-β1、基质金属蛋白酶(TIMP)-1表达的影响。方法:将84只清洁级SD大鼠随机分为7组,肝纤维化造模采用40%的四氯化碳/橄榄油腹腔注射,剂量为1ml/kg,每周2次,共4周。造模1周后给药。正常组与模型组大鼠用蒸馏水按20 ml/kg的量进行灌胃;其中养肝澳平高、中、低剂量组大鼠分别为28、14、7 g/kg,扶正化瘀组剂量为0.9 g/kg,秋水仙碱组剂量为1.0 mg/kg,每天按20 ml/kg灌胃给药1次,共给药8周。再检测大鼠血清生化指标、肝组织氧化物歧化酶(SOD)、丙二醛(MDA)、羟脯氨酸(HyP)含量、肝脏病理改变及TGF-β1、TIMP-1表达。结果:病理表现上模型组大鼠肝纤维化特征最明显,其余各组大鼠均有不同程度改善,养肝澳平高剂量组最轻;养肝澳平高、中剂量组SOD活力最高(P<0.01),MDA、HyP含量养肝澳平高剂量组明显降低(P<0.01);养肝澳平高剂量组TGF-β1、TIMP-1沉积显著减少(P<0.01),秋水仙碱组和扶正化瘀组能不同程度降低TGF-β1、TIMP-1水平(P<0.05),差异有统计学意义。结论:养肝澳平合剂有一定的抗脂质过氧化的作用,能够促进肝细胞的修复;并能降低HyP的含量,抑制胶原蛋白的生成减缓肝纤维化。

Objective:To study the effect of Yanggan Auping mixture in reversing the progress of liver fibrosis and its effect of the action of TGF-β1、TIMP-1.Methods:Eighty-four clean SD rats were randomly divided into 7 groups.Liver fibrosis was modeled by intraperitoneal injection of 40%carbon tetrachloride/olive oil at a dose of 1ml/kg twice a week for 4 weeks.The drug was given 1 week after the model was made and 8 weeks after the model was made.The normal group and the model group were given 20ml/kg of distilled water for gavage.The doses in the high,medium and low dose groups were given by 28,14 and 7 g/kg,respectively,those in the fuzheng huayu group were 0.9g/kg,and those in the colchicine group were 1.0 mg/kg.The dosage of 20ml/kg was given by gavage once a day for a total of 8 weeks.Then,serum biochemical indexes,SOD,MDA,Hyp contents,liver pathological changes,expression of TGF-β1 and TIMP-1 in rats were evaluated.Results:In terms of pathological manifestations,liver fibrosis was the most obvious in the model group,and the other groups were all improved to varying degrees,in which the liver high-dose group was the lightest.Yanggan Auping mixture in high,middle dose group significantly increased SOD activity(P<0.01),In MDA,HyP content level,Yanggan Auping mixture in high dose group is lowest(P<0.01),Yanggan Auping mixture in high dose group decreased TGF-β1,TIMP-1 deposition significantly(P<0.01),colchicine group and the FZHY group can reduced to some extent degrees TGF-β1,TIMP-1 level(P<0.05),the difference was statistically significant.