核因子-κB基因过度表达与肝细胞恶性转化的关系

Overexpression of hepatic nuclear-transcription factor κappaB gene association closely with the malignant transformation of rat hepatocytes

目的探讨核因子-κB(NF-κB)mRNA在肝癌(HCC)形成过程中的表达与动态改变。方法以2-乙酰氨基芴(2-FAA)喂饲雄性Sprague-Dawley(SD)大鼠诱发肝细胞癌变,以病理组织学(HE染色)观察肝细胞形态学的变化,以巢式逆转录聚合酶链反应(Nested-RT-PCR)扩增分析NF-κB mRNA表达,并定量分析肝细胞癌变过程肝组织中NF-κB的动态表达。结果SD大鼠在喂饲2-FAA后,肝细胞在形态学上出现颗粒样变性、癌前病变到HCC形成多个发展阶段。在HCC形成过程中,肝组织总RNA水平呈动态梯度增加,表现为癌变组>癌前组>变性组>对照组(P<0.01);肝组织NF-κB mRNA扩增的阳性率在变性组、癌前组和癌变组均为100%,明显高于正常对照组(P<0.01);肝组织中NF-κB呈明显的梯度增加,且与肝细胞的恶性转变呈正相关关系。结论肝癌形成过程中NF-κB mRNA过度表达,与肝癌发生、发展密切相关。

Objective To investigate the expression and dynamic alteration of hepatic nuclear-transcription factor κappaB （NF-κB） mRNA during hepatocellular carcinoma （HCC） formation.Methods Hepatoma model was induced with 2-fluorenylacetamide （2-FAA） on male Sprague-Dawley （SD） rats.Morphological changes of rat livers were observed by pathological examinations （HE staining）.Hepatic NF-κB mRNA was amplified by nested-RT-PCR,and the level of NF-κB expression was quantitively analyzed by ELISA,respectively.Results The hepatocytes of rats showed changes from granule-like degeneration to atypical hyperplasia to HCC development after induced with 2-FAA.In the course of HCC development,an dynamic-increasing tendency of hepatic total mRNA level was found from normal liver tissues to degeneration to precancerous to cancerous ones （P〈0.01）.The incidence of hepatic NF-κBmRNA were 100% in the tissues of degeneration,precancerous and cancerous rats,which was significantly higher than that in normal one （P〈0.01）.The increases of liver NF-κB expression were associated closely with the malignant transformation of rat hepatocytes.Conclusions The overexpression of NF-κBmRNA in rat heptocancerogenesis is closely related to the occurrence and development of HCC.