诱导性大鼠肝癌模型中HIF-1α、VEGF的表达

HIF-1alpha and VEGF expression in induced rat hepatocellular carcinoma model

目的探讨缺氧诱导因子-1α(HIF-1α)及血管内皮细胞生长因子(VEGF)在诱导性大鼠肝癌模型中的表达及其相关性。方法 70只SD大鼠分为模型组(60只)和正常对照组(10只),联合应用二乙基亚硝胺(DEN)和N-亚硝基吗啉(NMOR)诱发大鼠实验性肝癌,于诱癌第4、8、12、16周分批处死实验大鼠,常规制作肝脏病理切片。用免疫组织化学法检测大鼠肝脏癌变过程中不同时期的HIF-1α及VEGF的表达情况。结果实验第8、12、20周,模型组大鼠肝脏呈现典型的脂肪变性,炎性细胞浸润、肝硬化、肝癌的病理变化;肝脏HIF-1α及VEGF在大鼠肝脏癌变过程中表达明显增强(P<0.01);且HIF-1α与VEGF之间存在着显著正相关(r=0.953,P<0.01)。结论 HIF-1α及VEGF参与大鼠肝癌的发生与发展,其机制可能与HIF-1α、VEGF促进肿瘤血管生成有关。

Objective To explore the relationship between the expression of HIF-1α and VEGF in induced rat hepatocellular carcinoma model.Methods Seventy SD rats were devided randomly into two groups：model group （60 rats） and normal group （10 rats）.Hepatocellular carcinoma was induced with diethylnitrosamine （DEN） and N-nitrosomorpholine （NMOR） in the model group rats.The rats were sacrificed in batches at the 4th,8th,12th and 16th week of the experiment. Histological sections of liver tissues were made using routine methods. The expression of HIF-1α and VEGF proteins in the liver tissues was evaluated using immunohistochemical methods.Results Liver sections from the model group were typical pathological changes （steatosis, cell infiltration, cirrhosis and liver cancer）. The expression of HIF-1α and VEGF in those liver tissues was remarkably increased during the hepatocellular carcinogenesis （P〈0.01）. There was a direct correlation between the HIF-1α and VEGF （r=0.953,P〈0.01）.Conclusion HIF-1α and VEGF play a very important role in occurrence and development of hepatocellular carcinoma during rat hepatocellular carcinogenesis,the mechanism may be associated with the promotion of tumor angiogenesis.