大鼠实验性肝癌发生过程中存活素基因表达的动态观察

Dynamic expression of survivin during hepatocardnogenesis in rats

目的动态观察大鼠实验性肝细胞肝癌(HCC)不同发生发展阶段中存活素(survivin)基因的表达状态。方法采用免疫组织化学法和逆转录-聚合酶链反应(RT-PCR)法,检测大鼠HCC不同时期survivin的表达。结果黄曲霉毒素(AFB1)诱发大鼠HCC形成的最早时间在第46周,46周后,实验组存活的大鼠HCC发生率为54.9%(28/51),58周存活的大鼠HCC发生率为64.9%(24/37)。实验组HCC、癌旁肝组织survivin蛋白阳性率分别为41.7%和54.2%,两者差异无统计学意义(P>0.05)。而相应的大鼠,在46周之前及无肿瘤形成的大鼠和正常对照组无survivin蛋白表达。58周时,大鼠HCC中survivin mRNA的表达水平明显高于同期无肿瘤形成大鼠和正常对照肝组织(P均<0.01);相应癌旁肝组织亦明显高于同期无肿瘤形成大鼠和对照肝组织(P均<0.01);HCC与癌前活检肝组织比较,差异有统计学意义(P<0.01)。12、20、36和46周时,有肿瘤形成大鼠活检肝组织与正常对照组大鼠同期活检肝组织比较,survivin mRNA表达差异均有统计学意义(P均< 0.01)。结论survivin基因在HCC组织中高表达,提示该基因对HCC的发生发展起重要作用,检测HCC组织中survivin基因的表达,可能对HCC诊断有参考价值。

Objective To determine the dynamic expression of survivin gene in hepatoeareinogenesis of rats induced by aflatoxin B1 （AFB1）. Methods 78 Sprague-Dawley rats were used in this study. Hepatoeellular carcinoma was induced in the rats by aflatoxin B1. Liver and HCC tissues were examined by immunohistoehemistry and reverse transeriptase-polymerase chain reaction （RT-PCR）. Results The earliest hepatoeellular carcinoma occurred at 46^th week after AFB1 treatment. The HCC incidence was 54.9% （28/51） at 46^th week and 64.9% （24/37） at 58^th week. The positive rates of survivin protein expression in 24 HCC, para-eaneerous liver tissues of experimental group were 41.7% and 54.2%, respectively ,with no significant difference between them （P 〉 0.05 ）. No survivin expression was detected in the experimental group before 46^th week,neither in the rats without HCC occurrence nor the normal controls. The level of survivin mRNA expression in HCC at 58^th week was significantly higher than that in pre-HCC, no-HCC and normal liver tissues in the control group （P 〈0.01 ）. The level of survivin mRNA expression in para-eareinoma tissues was also significantly higher than that in no-HCC and normal liver tissues of the control （ P 〈 0.01 ）. The level of survivin mRNA in pre-HCC at 12^th ,20^th ,36^th ,46^th weeks were significantly higher than those in normal liver tissues taken from control group during the same periods （ P 〈 0.01 ）. Conclusion The over-expression of survivin gene is related to the occurrence of HCC and may play an important role in the carcinogenesis of HCC.