黄曲霉毒素B1诱导性大鼠肝癌超微结构、c—myc和HER-2表达变化

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，以及c—myc、HER-2mRNA表达变化规律。方法用AFB-（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，用RT—PCR技术检测不同病变肝组织中C—myc、HER-2mRNA的表达。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，典型肝细胞吞噬细胞现象；线粒体由增生肿胀到枯竭、空泡变；糖原颗粒逐渐减少等特征性变化。C—mycmRNA在损伤病变、早期癌变和癌变组织中表达水平均显著高于对照组大鼠肝组织（F=4．81，P=0．035；F=12．43，P=0．000；F=12．57，P=0．000）。HER-2mRNA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=10．89，P=0．001；后者F=11．48，P=0．000）；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，C—myc、HER-2异常表达参与AFB1诱导性大鼠早期肝癌的发生。

Changes in Expression of c- myc, HER- 2 Genes and Ultrastructure Observation on Aflatoxin B1 -induced Hepatocellular Carcinoma in Model in Rats

Objective To observe the uhrastructural morphology of hepatocytes and study the dynamic changes of mRNA expression for c - myc and HER - 2 on hepatocellular carcinoma（HCC） induced by aflatoxin B1 （ AFB1 ） in male Waster rats. Methods Male Waster rats HCC models were established by interval intraperitoneal injection of AFB1 （400μg/kg）. Uhrastructural morphology of liver tissues was observed by transmission electron microscopy, and mRNA expressions for c - myc and HER - 2 were detected by RT - PCR technology on difference stages of hepatocarcinogenesis. Results A series of characteristic changes were observed during the process of hepatocarcinogenesis in our rat model. For example, hepatocytes happened to hepatoxic lesion, changed into 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. On the other hand,the mRNA expression levels for c -myc were statistically higher in injured liver tissues, early cancerous tissues and HCC tissues when compared to normal liver tissues （ F = 4.81, P = 0.035, F = 12.43, P = 0. 000 and F = 12.57, P = 0. 000, respectively） ,and bath the differences in mRNA expression levels for HER- 2 were statistically significant between HCC or early cancerous tissues and normal livers or injured liver tissues （F = 10.89, P = 0. 001 and the latter, F = 11.48, P = 0.000）. Conclusions Hepatocytes happened to hepatoxic lesion, changed into atypical cells and cancerous cells during the AFB1 induced the process of hepatocarcinogenesis in our rat model, and abnormal increased expression of c - myc and HER - 2 mRNA may contribute to the pathogenesis of HCC at the early stage.