基质金属蛋白酶组织抑制因子mRNA及蛋白在肝硬化组织中的定位

目的：了解基质金属蛋白酶组织抑制因子TIMP－1和TIMP－2蛋白及mRNA在肝硬化组织中的表达和分布状态。方法：以抗TIMP－1和TIMP－2单克隆抗体及TIMP－1和TIMP－2 cDNA探针为试剂，采用免疫组织化学法和原位杂交技术检测肝硬化组织中TIMP－1和TIMP－2蛋白和mRNA，结果：40例肝硬化患者肝组织中TIMP－1和TIMP－2蛋白以及mRNA表达的阳性率为100％，TIMP－1阳性的组织TIMP－2亦为阳性，且TIMP－1强度高于TIMP－2，而正常肝组织未见阳性表达，TIMP－1和TIMP－2蛋白及mRNA表达的阳性信号均位于肝细胞胞浆中，细胞核中无表达，结论：肝硬化患者的肝细胞中存在TIMP－1和TIMP－2蛋白及mRNA的表达，其表达强度与肝组织病理改变呈正相关，这可能是通过抑制基质金属蛋白酶（MMPs)的活性，使得细胞外基质（ECM）降解减少而引起肝硬化。

Tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1 and TIMP-2) mRNA and antigens location in the liver of patients with cirrhosis

Objective To study the expression and distribution of TIMP 1 and TIMP 2 in liver tissue of cirrhosis patient and to investigate the roles and pathogenesis of TIMP 1 and TIMP 2 in liver cirrhosis. Methods TIMP 1 and TIMP 2 proteins and mRNA were detected with immunohistochemistry and in situ hybridization methods using monoclonal antibodies and cDNA probes. Results mRNA and proteins of TIMP 1 and TIMP 2 were detected in all the liver tissues from 40 liver cirrhosis patients, all in cytoplasm but not nucleus. TIMP 1 and TIMP 2 were found co exist in all samples, while TIMP 1 concentration was higher. Conclusions mRNA and protein of TIMP 1 and TIMP 2 are found in all the cirrhosis patient samples. Liver TIMP 1 and TIMP 2 concentrations increase with the progression of liver cirrhosis, decrease the degradation of extracellular matrix proteins, resulting in the initiation and the development of liver fibrosis and liver cirrhosis.