二乙基亚硝胺诱发大鼠肝细胞癌发生过程中基质金属蛋白酶动态变化

Dynamic changes of matrix metalloproteinases in liver tissue during the development of diethylnitrosamine-induced rat hepatocarcinoma

目的研究基质金属蛋白酶(MMPs)在肝细胞癌形成过程中动态变化及作用方法采用二乙基亚硝胺(DENA)诱癌建立大鼠肝癌模型.应用明胶酶谱法测定诱癌过程中癌变发生的三个阶段6个时相肝组织中MMP-2和MMP-9的表达及活性.结果肝癌发生过程中基质金属蛋白酶呈持续升高的趋势,至早期癌变期及肿瘤演进期(16wk～24wk)MMP-2,MMP-9的表达呈一个较高的平台(分别为167350±20436和237754±32675),且发现MMP-2的活性形式表达显著增加.结论 MMPs的表达不同与肝星状细胞的激活和肝细胞癌形成有关,而与肿瘤的结节数及大小无关.

AIM To study the dynamic changes of the latent and activated forms of MMP-2 and MMP-9 in rat liver tissue during experimental hepatocarcinogenesis. METHODS Hepatocellular carcinomas were induced with the administration of diethy Initrosoamine (DENA) in rats. Gelatin zymography was used for the detection of latent and activated forms of MMP-2 and MMP-9 in six phases of three carcinogenic successive stages, these are, the non- specific changes reacting to the drug toxicity, the precancerous lesions and the lesions of hepatocellular carcinoma. RFSULTS The expression of MMP-2 and MMP-9 were increased throughout hepatocarcinogenesis; overexpression of MMP-2 and MMP-9 in the first two stages, and the expression reached their maximum in the 16th week ( 167350 ± 20436 and 237754 ± 32675 respectively), with the activation of MMP-2 appearing to be a feature of the HCC. CONCLUSION The different expression of MMP-2 and MMP-9 may be due to Ito cell activated by the various inflammatory cytokines and the hepatocarcinogenesis, but independent of the number and volume of the neoplastic nodules.