大鼠肝脏癌变过程中环氧合酶-2表达与肿瘤血管生成的关系

目的 探讨环氧合酶2（COX-2）表达与肝癌血管生成之间的关系。方法 将40只Wistar大鼠分为模型组（30只）和正常对照组（10只），用0．01％二乙基亚硝胺（DEN）诱发大鼠实验性肝癌，于诱癌第6、12、18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COX-2、血管内皮生长因子（VEGF）及其受体2（VEGFR2／KDR）、基质金属蛋白酶-2（MMP-2）和微血管密度（MVD）的表达情况。结果 实验第6、12、18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COX-2、VEGF、KDR、MMP-2在大鼠肝脏癌变过程中表达明显增强；MVD值在肝癌期明显升高，MVD与VEGF、KDR、MMP-2之间存在着显著的正相关（r值分别0．858、0．788、0．684，P值均〈0．01），COX-2表达与VEGF、KDR、MMP2及MVD值之间也均具有显著的正相关性（r值分别为0．771、0．599、0．690、0．788，P值均〈0．01）。结论 COX-2在大鼠肝脏癌变过程中具有促进肿瘤血管生成的作用，这可能是COX-2导致肿瘤发生与发展的重要机制之一。

A relationship between cyclooxygenase-2 expression and tumor angiogenesis in experimental rat liver carcinogenesis

Objective To explore the relationship between the expression of cyclooxygenase-2 (COX-2) andangio-genesis in hepatocellular carcinoma. Methods Forty Wistar rats were divided into two groups: a model group (30 rats) and a normal group (10 rats). Hepatocellular carcinoma was induced with 0.01% diethylnitrosamine (DEN) in the model group rats. The rats were sacrificed in batches at the 6th, 12th and 18th week of the experiment. Histological sections of liver tissues were made using routine methods. The expressions of COX-2, VEGF, VEGFR-2/KDR, and MMP-2 protein in the liver tissues were evaluated using immunohistochemical methods. Results In liver sections from the model group there were marked pathological changes (steatosis, cell infiltration, cirrhosis and liver cancer). The expressions of VEGF, VEGFR-2/KDR, and MMP-2 in those liver tissues were remarkably increased during the hepatocellular carcinogensis. Microvessel density (MVD) was also obviously raised during the process of the cancer development. There was a direct correlation between the MVD and VEGF/KDR/MMP-2 (r = 0.858, 0.788, 0.684, respectively; all P < 0.01). There was also a direct correlation between the COX-2 and VEGF/KDR/ MMP-2/MVD (r = 0.771,0.599, 0.690,0.788, respectively; all P < 0.01). Conclusion COX-2 can promote tumor angiogenesis during rat hepatocellular carcinogenesis. This may be one of the mechanisms in which COX-2 promotes carcinomas.