苦碟子注射液对大鼠肝纤维化模型肝脏MMP-1、TIMP-1的影响

目的观察肝纤维化形成过程中肝组织MMP-1、TIMP-1表达,以探讨MMP-1、TIMP-1与基质转换的关系,以及苦碟子注射液和大黄虫丸对它们的影响。方法将大鼠随机分为正常对照组、模型对照组与苦碟子注射液高剂量组、苦碟子注射液低剂量组和大黄虫丸组,采用40%CC l4橄榄油溶液造模(0.15 mL/100 g),2次/周,并从实验第3周开始给大鼠用20%乙醇灌胃(1 mL/100 g),隔天1次造模。造模结束给予苦碟子注射液高低剂量和大黄虫丸治疗,12周末在股动脉处取血,取肝脏标本。采用HE方法检测模型对照组和各给药组病理变化情况、血清PCⅢ水平变化。免疫组织化学法检测肝组织MMP-1、TIMP-1。结果模型对照组及各给药组与正常对照组比较均呈程度不同的病理损害,MMP-1、TIMP-1表达均显著增高(P均0.05),且TIMP-1表达明显高于MMP-1表达。各给药组与模型对照组比较,MMP-1表达均无显著性差异(P均0.05),TIMP-1表达却均明显减少(P均0.05)。结论肝脏炎症活动及纤维化会出现程度不同的病理损害,可能与MMP-1及TIMP-1表达明显失衡有关。苦碟子注射液及大黄虫丸治疗对其有一定的抑制作用。

Study of Kudiezi injection on MMP-1 and TIMP-1 in liver of model rats with hepatic fibrosis

Objective It is to observe the expression of MMP-1 and TIMP-1 in liver tissue in the process of hepatic fibrosis and then to approach the relation of MMP-1 and TIMP-1 with ground substance transition and the influence of Kudiezi injection and Dahuang Zhechong pill on them.Methods The rats were divided into normal control group,model control group,Kudiezi injection high dose group,Kudiezi injection low dose group and Dahuang Zhechong pill group.40% CCl4 olive oil solution 0.15 mL/100 g were used to make model for twice a week.From the third week after experiment,the rats were given 20% alcohol 1 mL/100 g intragastric administration quaque die alterna.At the end of making model,the rats were treated with Kudiezi injection and Dahuang Zhechong pill.At the end of the twelfth week,the blood of the rats was taken from femoral artery and the liver specimens were taken.The pathological changes and the changes of serum PC Ⅲ level in the rats were detected with HE method.MMP-1 and TIMP-1 in liver tissue were detected with immunohistochemical method.Results Compared with normal control group,different degree of pathological injury were discovered in model control group and all medication administration groups,the expression of MMP-1 and TIMP-1 were all significant heightened(all P <0.05) and the expression of TIMP-1 was obviously higher than the expression of MMP-1.Compared with model control group,the expression of MMP-1 in all medication administration groups had no significant differences(all P >0.05) but the expression of TIMP-1 was obviously decreased(all P <0.05).Conclusion Liver inflammation and hepatic fibrosis can induce different degree of pathological injury,which may be concerned with obvious unbalance of the expressions of MMP-1 and TIMP-1.Kudiezi injection and Dahuang Zhechong pill have determinate inhibitory action on it.