诱导型一氧化氮合酶和血管内皮生长因子在地鼠颊囊癌变中的表达及意义

Expression and Significance of Inducible Nitric Oxide Synthase and Vascular Endothelial Growth Factor in Carcinogenesis of Hamster Cheek Pouch

背景与目的:诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)和血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)都被认为与肿瘤发生发展有关。本实验研究iNOS、VEGF地鼠颊囊癌变中的表达及其与肿瘤血管形成的关系,为进一步抑制肿瘤微血管形成提供依据。方法:50只金黄地鼠分成2组,40只作为实验组,用0.5%二甲基苯并蒽(9,10-dimethyl-1,2-benz-anthracene,DMBA)丙酮液涂布地鼠右侧颊囊粘膜,在实验第6、9、12、16周末各处死10只;另外10只金黄地鼠作为对照组,不涂布DMBA丙酮液,在第16周末处死。应用免疫组化法检测地鼠颊囊癌变过程中iNOS、VEGF的表达,抗Ⅷ因子多克隆抗体显示血管内皮细胞,根据阳性染色的血管内皮细胞计数微血管密度,硝酸还原酶法测定一氧化氮(nitricoxide,NO)的量的变化。结果:iNOS和VEGF在正常地鼠颊囊粘膜上皮呈阴性,从第6周开始到第16周iNOS、VEGF出现阳性表达并渐渐增强(P<0.05),各组之间总体差异有显著性;从第6周到第16周实验组各组间NO的量不断增加(P<0.05),差异有显著性;在iNOS和VEGF表达阳性组MVD显著高于iNOS和VEGF阴性组。结论:NO和VEGF在地鼠颊囊癌的发生发展中起促进作用,NO与VEGF在肿瘤血管生成中起密切关系。

BACKGROUND ＆ OBJECTIVE. Inducible nitric oxide synthase （iNOS） and vascular endothelial growth factor （VEGF） are related to carcinogenesis and development of tumors. This study was to explore the correlations of the expression of iNOS and VEGF to the angiogenesis in carcinogenesis of Golden hamster cheek pouch. METHODS： A total of 50 Golden hamsters were divided into 2 groups： 40 in experiment group, 10 in control group. DMBA was painted on the cheek pouches of the hamsters in experiment group, but not in control group. The hamsters in experiment group were killed at the 6th, 9th, 12th, and 16th weeks, respectively; 10 at each time. The hamsters in. control group were killed at the 16th week. The expression of iNOS and VEGF and microvessel density （MVD） in carcinogenesis in the pouches of hamsters were detected by SABC immunohistochemistry; the level of nitric oxide （NO） was measured by spectrophotometry. RESULTS. Both iNOS and VEGF expression were negative in the pouches of the hamsters in control group, but they increased gradually from the 6th to 16th week in exprement group （P〈0.05）. The level of NO increased from the 6th to 16th week, too, and the difference between each 2 groups was significant （P〈0.05）. MVD was significantly higher in iNOS- and VEGF-positive group than in iNOS- and VEGF-negative group （P〈 0.05）. CONCLUSIONS. NO plays an important role in the carcinogenesis of Golden hamster cheek pouch, iNOS and VEGF may exert interactions in tumor angiogenesis.