二乙基亚硝胺诱发大鼠肝细胞癌发生过程中的基质金属蛋白酶动态变化

目的 研究基质金属蛋白酶（MMPs)在肝细胞癌形成过程中的动态变化及作用。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（16-24周）MMP-2，MMP-9的表达呈一个较高的平台，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。

Dynamic changes of matrix metalloproteinases in liver tissue during deveopment of diethylnitrosamine-in-duced rat hepatocellular carcinoma

Objective To study the dynamic changes of the latent and activated forms of MMP 2 and MMP 9 in rat liver tissue during experimental hetocarcinogenesis. Methods Hepatocellular carcinoma (HCC) was induced with the administration of diethyl nitrosoamine (DENA) in rats. Gelatin zymography was used to detect latent and activated forms of MMP 2 and MMP 9 in 6 phases of three carcinogenic successive stages including the non specific changes reacting to the drug toxicity, the procancerous lesions and the lesions of HCC. Results The expression of MMP 2 and MMP 9 was enhanced throughout the hepatocarcinogenesis. Overexpressin of MMP 2 and MMP 9 was found in the first 2 stages, and the expression reached its peak in the 16th week. The activation of MMP 2 appeared to be a feature of HCC. Conclusions Different expression of MMP 2 and MMP 9 may be due to Ito cell activated by various inflammatory cytokines and the hepatocarcinogenesis but independent of the number and volume of the neoplastic nodules.