目的:观察铜锌-超氧化物歧化酶(CuZn-SOD)mRNA和蛋白在黄曲霉毒素B1(AFB1)诱发树的肝细胞癌(HCC)形成过程中的表达变化,并对其在人肝癌组织中的表达情况进行验证和对比,探讨CuZn-SOD在肝癌形成中的作用。方法:应用逆转录多聚酶链反应(RT-PCR)和免疫组化方法检测35例AFB1诱发的树鼩肝癌、癌旁以及这些动物癌发生前自身的活检肝组织和相应对照组织中CuZn-SOD基因在mRNA水平和蛋白水平的表达情况,并且在35例人肝癌和癌旁组织进行验证。结果:CuZn-SOD mRNA和蛋白在树鼩肝癌组织的表达水平不仅明显低于癌旁及癌前组织,也明显低于实验组虽经AFB。处理但最终未发生肝癌的动物以及正常对照动物的同期活检肝组织。人肝癌组织的CuZn-SOD mRNA和蛋白表达情况与树鼩相似,癌组织的阳性表达率和表达水平均明显低于癌旁组织,并且分化较低的肝癌组织的蛋白表达水平下调更显著。结论:CuZn-SOD可能是肝癌发生的相关基因之一,它在mRNA水平和蛋白水平的表达下降与肝癌的发生发展可能互为因果。
Objective:To elucidate the change of CuZn-SOD in aflatoxin B I(AFB 1) induced human hepatocellular carcinoma (HCC) by observing the its mRNA and protein expression and comparing it with human HCC. Methods:CuZn-SOD mRNA and protein expression were detected by reverse transcriptase polymerase chain reaction and immunohistochemical staining in HCC,para-HCC,and pre HCC tissues from 35 cases of tree shrews' HCC induced by AFB-1, as well as corresponding control tissues. The results were verified in the HCC and para-HCC tissues from 35 cases of human HCC. Results: The CuZn-SOD mRNA and protein expression in tree shrews' HCC tissues was not only significantly lower than that in para HCC and pre HCC tissue but also lower than that in liver tissues from non-HCC animals after AFB-1 treatment and control groups (all P〈0.01). Both the positive rate and general score of CuZn-SOD mRNA and protein expression in human HCC tissues were significantly lower than that in para-HCC tissues (P〈0.001 ). Low differentiation stage was associated with down regulation of CuZn-SOD protein expression in human HCC tissues. Conclusion: CuZn-SOD might be one of the principal genes related to HCC. Likely, there might exist a relationship between the down-regulation of CuZn-SOD and hepatocarcinogenesis.