3种小鼠肝纤维化模型的比较及凯时注射液的抗肝纤维化作用评价

Comparative study of different animal models of hepatic fibrosis reproduced by different drugs and evaluation of effect of Kaishi injection in prevention of fibrosis

目的对3种不同药物诱导产生的小鼠肝纤维化模型进行筛选,并选用最佳模型评价凯时注射液的抗肝纤维化作用。方法将BALB/c小鼠分别经腹腔注射二甲基亚硝胺(DMN)、硫代乙酰胺(TAA)及四氯化碳(CCl4)三种药物诱导产生不同的小鼠肝纤维化模型,以肝组织病理学变化和血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)及透明质酸(HA)浓度为指标筛选出最优模型,对最优模型小鼠尾静脉注射凯时注射液,评价其抗肝纤维化作用。结果与正常对照组比较,TAA组小鼠的体重无明显变化,而DMN组、CCl4组小鼠体重明显下降(P<0.05)。与正常对照组相比,3个实验组小鼠均出现显著肝纤维化(P<0.001),同时血清中ALT、AST和HA含量明显升高(P<0.001),且DMN组小鼠肝纤维化程度及血清ALT、AST、HA含量均高于其他两组(P<0.05)。DMN诱导的小鼠肝纤维化模型经凯时注射液治疗后,肝组织纤维化指标及血清中AST、ALT和HA含量改变均显著逆转(P<0.05)。结论 DMN诱导的小鼠肝纤维化模型成功率高、建模稳定。凯时注射液在小鼠体内有较好的抗肝纤维化作用。

Objective To screen the best animal model of hepatic fibrosis reproduced by different drugs and to evaluate the anti-fibrosis activity of Kaishi injection in the chosen animal model.Methods Normal saline（NS）,dimethyl nitrosamine（DMN）,thiacetamide（TAA） or carbon tetrachloride（CCl4） was administered respectively to the randomly grouped BALB/c mice intraperitoneally in an identical dosage.Five weeks later,the best animal model was screened based on the changes in concentration of alanine aminotransferase（ALT）,aspartate aminotransferase（AST） and hyaluronic acid（HA） in the plasma of the above 3 animal models,then the model of most obvious hepatic fibrosis was employed to investigate the anti-fibrosis activity of Kaishi injection.Results The body weight in TAA group was not significantly different from that of control group.However,the respective body weight of CCl4 and DMN groups decreased significantly compared with that of control group（P0.05）.The degree of liver fibrosis and plasma concentrations of ALT,AST and HA in the 3 model groups were all higher than that of control group（P0.001）.Plasma concentrations of ALT,AST and HA in DMN group were higher than that of other groups（P0.05）,DMN group was therefore chosen as the model for experimental group.After the treatment with Kaishi injection,alleviation of liver fibrosis and reduction in levels of ALT,AST and HA in plasma were found（P0.05）.Conclusions DMN treatment was proved to be the most promising method to successfully induce hepatic fibrosis in BALB/c mice.Kaishi injection has been shown as to have a good therapeutic effect on DMN induced hepatic fibrosis in mice.