二甲基亚硝胺肝纤维化过程中金属蛋白酶组织抑制因子1基因表达的动态变化

目的：观察肝纤维化过程中TIMP－1基因表达的动态变化，探讨肝纤维化的发生发展机理，以及中药复方861的抗纤维化机制。方法：100只Wistar大鼠随机分为正常对照组、模型组和复方861预防组。模型组用二甲基亚硝胺（DMN）腹腔内注射诱导大鼠发生肝纤维化，共计6周，第1周注射3次，其它周均注射2次，观察8周；复方861预防组大鼠则在用DMN腹腔注射的同时，每天接受中药灌胃1次，直至实验结束；政党对照组以生理盐水代替DMN腹腔内注射。分别于第1、4、10、17、28、42、56天分批处死动物，取出肝脏，以半定量RT－PCR法检测肝组织中TIMP－1 mRNA。结果：从动态发展来看，正常对照组大鼠肝组织TIMP－1 mRNA的表达水平基本稳定不变；模型组大鼠肝组织TIMP－1 mRNA的表达从第4天开始升高，10天后一直维持高水平表达直至动物实验结束；复方861预防组TIMP－1 mRNA的表达变化不大。从组间比较来看，模型组肝组织TIMP－1 mRNA的表达水平从第4天开始即比正常对照组明显增高，此后升高更显直至实验结束；861预防组从第10天开始比正常对照组有所增高，但比模型组明显低，从28天开始以后则比模型组降低越发显。结论：TIMP－1的表达在肝纤维化的发展过程中逐渐增高。它以抑制纤维胶原降解，因而在促进肝纤维化发展的进程中起重要作用。中药复方861具有抑制TIMP－1表达的作用，这是其抗纤维化的机制之一。

Dynamic change of tissue inhibitor of metalloproteinases-1 messenger RNA expression during dimethylnitrosamine induced liver fibrosis

Objective To observe the dynamic change of tissue inhibitor of metalloproteinase-1 messenger RNA expression during experimental liver injury and fibrosis ,and explore the developmental principle of liver fibrosis and the antifibrotic mechanism of herbal compound 861(Cpd861). Methods One hundred of Wistar rats were randomly divided into normal control group, model group and Cpd 861 prophylactic group. In the model group, rats were intraperitoneally injected with dimethylnitrosamine (DMN). In the normal control group, rats were treated with normal saline by the same method as former. In the Cpd 861 prophylactic group, rats were fed with Cpd 861 while treated with DMN. Animals were sacrificed on 1, 4, 10, 17, 28, 42, 56 days after injection. TIMP-1 mRNA expression was detected by RT-PCR. Results From the dynamic prospect, TIMP-1 mRNA expression level almost kept unchanged in normal control group, while initially increased from 4th days and constantly kept higher level from 10th days to the end of experiment in the model group, and presented little change in the Cpd 861 prophylactic group. Between the different groups, from 4th days to the end of experiment, TIMP-1 mRNA expression level was more and more significantly higher in the model group than the normal group, while, from 10th days to the end, was slightly higher in the Cpd 861 prophylactic group than the normal group, and it was more and more obviously lower in the Cpd 861 prophylactic group than the model group. Conclusion TIMP-1 mRNA expression level is more and more higher during the whole course of liver fibrosis. TIMP-1 can promote the process of liver fibrosis because of its inhibitory activity against the degradation of fibrillar collagen. Inhibiting the expression of TIMP-1may be one of the antifibrotic mechanism of Cpd 861.