血管内皮生长因子动态表达及干预对肝细胞癌变的影响

目的 动态观察癌变过程中血管内皮生长因子(VEGF)改变及表达干预对肝细胞癌(HCC)发生的影响.方法 将SD鼠数字随机分为诱癌组、诱癌干预组和对照组,前两组以含2-乙酰氨基芴(0.05%)的颗粒饲料喂饲诱发肝癌,诱癌干预组同时以沙利度胺(100 mg/kg体重)灌胃.分期、分批处死实验鼠与对照鼠,以病理学、免疫组化、Western印迹及ELISA分析VEGF表达及相互关系.结果 诱癌后肝细胞出现颗粒样变性、不典型增生及HCC的变化;阳性VEGF呈棕黄色颗粒,存在胞质,偶见于胞核;VEGF表达率和VEGF/β-肌动蛋白比率分别为:对照组25%和0.16±0.02、肝细胞变性组88.9%和0.29±0.04、癌前病变组100%和0.52±0.03及癌变组100%和0.84±0.02;VEGF表达随组织学改变呈梯度增加,癌变组明显高于对照组和肝细胞变性组(P<0.05);肝组织与血VEGF动态改变呈显著正相关(r=0.785,t=8.00,P=0.000);干预组VEGF表达及肝癌发生率均显著低于诱癌组.结论 VEGF异常与肝癌发生发展有关,抑制肝VEGF表达、可推迟肝细胞癌变的发生.

Dynamic alterations of VEGF and intervention of its expression on effect of hepatocyte malignant transformation

Objective To investigate the influences of VEGF expression through the intervention of thalidomine in malignant transformation of hepatocytes. Methods Hepatoma model was induced with 2-fluorenyl-acetamide (2-FAA, 0. 05%) in male SD rats. And thalidomide was administered intragastrically to block the progress of hepatoma. Some rats were sacrificed at a fortnightly interval. Morphological changes were observed by pathological examinations (HE staining). The VEGF expressions in rat liver tissues were detected by ELISA and immunohistochemistry respectively. Results Hepatocytes in rats fed with 2-FAA showed vacuole-like denaturations at an early stage, dysplastic nodules appeared at a middle stage and finally progressed to tubercles of cancerous nest. All were the manifestations of highly differentiated hepatocellular carcinoma (HCC). An increasing tendency of hepatic VEGF protein was found for normal liver to precancerous to cancerous tissues during the development of hepatoma. The VEGF levels in hepatoma were significantly higher than those in normal ones. Thalidomine repressed the morphologic change of hepatic cells. And the VEGF level of thalidomide group was lower than those in 2-FAA group. Conclusion Thalidomide can inhibit the hepatic VEGF expression and arrest the development of rat hepatoma.