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目的观察肝细胞癌变过程中胰岛素样生长因子Ⅱ(IGF-Ⅱ)及IGF结合蛋白3(IGFBP-3)的动态表达特征。方法以2-乙酰氨基芴(2-FAA)喂饲雄性SD鼠诱发肝细胞肝癌(HCC)发生,分别观察肝细胞形态学、肝脏及血清IGF-Ⅱ的动态变化和肝细胞浆IGFBP-3蛋白水平变化。以免疫组织化学法观察鼠肝组织中IGF-Ⅱ表达,分析IGF-Ⅱ表达与IGFBP-3蛋白水平变化及其病理学特征在HCC发生过程中的关系。结果诱癌过程肝细胞出现颗粒样变性、不典型增生到HCC的形成过程中IGF-Ⅱ呈梯度表达,表现为癌变组明显高于正常组和变性组(P<0.01)。癌变过程中IGF-Ⅱ呈阳性表达和胞内分布,肝脏和血清IGF-Ⅱ呈显著正相关。肝细胞浆IGFBP-3的表达水平随肝组织学形态的改变呈降低趋势,表现为癌变组明显低于变性组和正常组(P<0.01),且有低于癌前病变组(癌前组)趋势。结论IGF-Ⅱ及IGFBP-3过表达与HCC的发生、发展有关,可成为HCC早期诊断的标志。
Objective To observe the dynamic expression of insulin-like growth factor Ⅱ (IGF-Ⅱ) and IGF-3 (IGFBP-3) during hepatocellular carcinogenesis. Methods Male SD rats were induced by 2-FAA (2-FAA) to induce hepatocellular carcinoma (HCC). The morphological changes of hepatocytes, the dynamic changes of hepatic and serum IGF-Ⅱ and IGFBP-3 Horizontal changes. Immunohistochemistry was used to observe the expression of IGF-Ⅱ in rat liver tissue. The relationship between the expression of IGF-Ⅱ and the level of IGFBP-3 protein and pathological features of HCC was analyzed. Results The hepatocellular granulocyte degeneration was observed during the process of carcinogenesis. The expression of IGF-Ⅱ in the process of atypical hyperplasia to HCC was graded, which showed that the expression of IGF-Ⅱ in the carcinogenesis group was significantly higher than that in the normal group and the degeneration group (P <0.01). IGF-Ⅱ was positively expressed and intracellularly distributed during carcinogenesis, and there was a significant positive correlation between liver and serum IGF-Ⅱ. The expression level of IGFBP-3 in liver cytoplasm decreased with the change of liver histology, showing that the expression of IGFBP-3 in hepatocellular plasma was significantly lower than that in degenerative group and normal group (P <0.01), and lower than that in precancerous lesion group )trend. Conclusion The overexpression of IGF-Ⅱ and IGFBP-3 is related to the occurrence and development of HCC, which may be the marker of early diagnosis of HCC.