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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 2cDNA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10 0 % ,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。
Objective To investigate the expression and distribution of TIMP-1 and TIMP-2 protein and mRNA in cirrhosis of the liver. Methods The anti-TIMP1 and TIMP2 monoclonal antibodies and TIMP1 and TIMP2 cDNA probes were used as reagents to detect TIMP-1 and TIMP-2 protein and mRNA in cirrhotic tissues by immunohistochemistry and in situ hybridization. Results The positive rate of TIMP-1 and TIMP-2 protein and mRNA expression in 40 cirrhotic patients was 100%, TIMP-2 was also positive in TIMP-1-positive tissue and TIMP-1 was higher in TIMP-1 than in TIMP-2 No positive expression. The positive signals of TIMP-1 and TIMP-2 protein and mRNA expression were located in the cytoplasm of hepatocytes without expression in the nucleus. Conclusions The expression of TIMP-1 and TIMP-2 protein and mRNA in liver cells of patients with cirrhosis is positively correlated with the pathological changes of liver tissue, which may be due to inhibition of the activity of matrix metalloproteinases (MMPs), making the extracellular matrix ( ECM) reduce the degradation caused by cirrhosis.