免疫诱导型和CCl_4诱导型大鼠TIMP-1表达水平的差异及与肝纤维化程度相关性

Differentia of the correlation between the TIMP-1 expression level and hepatic fibrosis in immune-induced rat liver fibrosis model and CCl_4-induced rat liver fibrosis model

目的探讨免疫诱导型和CCl4诱导型大鼠肝纤维化模型制备过程中基质金属蛋白酶组织抑制因子1(TIMP1)表达水平与肝纤维化程度相关性的差异。方法双夹心ELISA法定量监测免疫诱导和CCl4诱导大鼠肝纤维化模型制备过程中大鼠血清TIMP1水平,与常规病理学检查分级,进行相关性分析,并进一步用原位杂交法观察TIMP1mRNA在两种肝纤维化模型中的表达差异。结果免疫诱导型大鼠肝纤维化模型制备过程中其血清TIMP1水平能较好的反映肝纤维化程度,原位杂交显示TIMP1mRNA表达较强;CCl4诱导型模型制备过程中其血清TIMP1水平与肝纤维化程度相关性无统计学意义,原位杂交显示TIMP1mRNA表达较弱,且在同等级纤维化程度肝组织中表达差异较大。结论免疫诱导大鼠肝纤维化模型病变有一定发展过程,分期明显,血清TIMP1水平能较好的反应其肝纤维化程度;CCl4诱导型大鼠肝纤维化模型病变过程较快,分期不明显,血清TIMP1水平不能作为其肝纤维化程度的指标。

Objective To explore the difference of the correlation between the TIMP-I expression level and hepatic fibrosis in rat liver fibrosis models induced separately by HSA （human sreum albumin） and CC14. Methods The serum TIMP- 1 level of experiment rats in the model induced process was detected with ELISA and compared with the results of histopathological grading of liver biopsy, in order to determine whether the serum TIMP-1 level in the two rat fibrosis models could reflect the severity of hepatic fibrosis. Furthermore., in situ hybridization was used to determine the expression difference of TIMP-1 mRNA in the two models. Results The serum TIMP-1 level in immune - induced rat liver fibrosis model can reflect the severity of hepatic fibrosis and the positive in situ hybridization signal of TIMP-1 mRNA is strong; In CCl4 - induced rat liver fibrosis model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis is insignificant in statistics. And compared with immune- induced rat liver fibrosis model, the positive in situ hybridization signal of TIMP-1 mRNA is weaker, while the expression variation is higher for the same severity of hepatic fibrosis. Conclusion Process of pathological changes of immune-induced rat liver fibrosis model is gradual and serum TIMP-1 level can reflect the severity of fibrosis. CCl4 - induced rat liver fibrosis model developed faster in comparison with immune-induced rat liver fibrosis model and no significant correlation exists between serum TIMP-1 level and the severity of fibrosis.