黄曲霉毒素B1诱导性大鼠肝癌超微结构观察及N-ras表达变化  

Changes of ultrastructure and N-ras gene expression in aflatoxin B1-induced hepatocellular carcinoma in rat model

作　　者：张友才[1] 陈金霞[1] 董培红[1] 陈迎晓[1] 陈永平[1] 王晓东[1] 李剑敏[1] 方周溪[2] 

机构地区：[1]温州医学院附属第一医院,浙江温州325005 [2]温州医学院

出　　处：《中国预防医学杂志》2010年第7期671-674,共4页Chinese Preventive Medicine

基　　金：浙江省自然科学基金资助项目(Y207542);温州市科技计划项目(Y20070025)

摘　　要：目的探讨黄曲霉毒素B1(AFB1)诱导性大鼠肝癌模型超微病理特征及N-rasmRNA表达变化规律。方法 40只Wistar大鼠分为正常对照组(12只)和诱癌组(28只)用AFB1(400μg/kg)间断腹腔注射雄性Wistar大鼠制作肝癌模型,电镜观察大鼠肝组织超微结构。应用RT-PCR技术检测对照组大鼠肝组织,损伤病变、早期癌变和癌变肝组织中N-ras mRNA表达水平。结果本组大鼠肝癌模型中,肝细胞呈变性损伤,异型性到癌变;线粒体由增生肿胀到枯竭、空泡变;糖原颗粒呈逐渐减少等特征性变化。观察到典型肝细胞吞噬细胞现象。N-rasmRNA在早期癌变组织、癌变组织中表达水平均显著高于对照组大鼠肝组织和损伤病变肝组织(F=5.47,P=0.019;后者F=6.98,P=0.006)。结论 AFB1诱导性大鼠肝细胞出现变性、异型性及癌细胞渐变的超微结构特征,N-ras异常表达参与大鼠肝细胞癌变机制。Objective To observe the ultrastructural morphology of hepatocytes and study the dynamic changes of mRNA expression of N-ras gene on hepatocellular carcinoma（HCC） induced by aflatoxin B1 （AFB1） in male Wistar rats.Methods The HCC model of male Wistar rats was established by interval intraperitoneal injection of AFB1（400 μg/kg）.Ultrastructural morphology of liver tissues was observed by transmission electron microscopy,and mRNA expression of N-ras gene was detected by RT-PCR technology for normal liver tissues,injured liver tissues,early cancerous and HCC liver tissues,respectively.Results A series of characteristic hepatoxic lesion changes were observed during the process of hepatocarcinogenesis in our rat model in cluding occurrences of atypical cells and cancerous cells.Mitochondria proliferated and swelled at early stage of hepatocarcinogenesis,then vanished and altered to vacuole structure at later stage.Hepatin grains were abundant at early stage,but decreased gradually.We also observed that hepatocytes phagocytized other cells during the process of hepatocarcinogenesis.The differences in mRNA expression levels of N-ras were statistically significant between HCC or early cancerous liver tissues and normal livers,and also injured liver tissues（F=5.47,P=0.019 and the latter,F=6.98,P=0.006）.Conclusion The hepatoxic lesion,formation of atypical and cancerous cells of hepatocytes were observed during the AFB1 induced process of hepatocarcinogenesis in the rat model.The increased expression of N-ras mRNA may contribute to the pathogenesis of HCC.

关 键 词：肝癌 超微结构 N-RAS基因 黄曲霉毒素B1 

分 类 号：R735.7[医药卫生—肿瘤]