【摘要】 目的：观察化学致癌物诱发大鼠肺鳞癌癌变过程中间质微血管密度（microvessel density,MVD）变化及血管内皮细胞生长因子（vascular endothelial growth faetor,VEGF）及其受体（FLK-1）表达的变化，探讨上述指标与肺癌发生发展的关系。方法：Wistar大鼠80只，其中70只用致癌质碘油溶液左肺叶支气管灌注，10只对照。第15～75天分批处死动物，取左肺组织。应用免疫组织化学S-P法检测大鼠肺鳞癌癌变各阶段组织的VEGF、FLK-1的蛋白表达，在vWF染色切片上检测MVD。结果：随大鼠肺鳞癌的发生发展，VEGF、FLK-1表达均逐渐增强，MVD计数逐渐增高。不典型增生MVD（8.92±3.80）、VEGF阳性系数（1.25±0.95），原位癌MVD（39.5±12.6）、VEGF（2.25±1.07），早期浸润癌MVD（58.5±18.4）、VEGF（3.03±0.93）之间比较，其差异分别具有高度显著性(P< 0.01)。原位癌FLK-1阳性系数（2.00±0.93）和早期浸润癌FLK-1阳性系数（2.63±1.54）比较，其差异具显著性（P< 0.05）。VEGF表达与MVD（r=0.983 7，P< 0.01）和FLK-1表达（r=0.968 8，P< 0.01）呈高度正相关。FLK-1在肿瘤细胞、血管内皮细胞及血管平滑肌细胞内都有表达，且在肿瘤细胞内的表达强度高于血管内皮细胞。结论：新生血管形成是大鼠肺鳞癌发生发展的重要更多还原

【Abstract】 Objective：The aim of this study was to investigate the role of vasculature，vascular endothelial growth factor(VEGF), and its receptor(FLK-1) during lung carcinogenesis in Wistar rats. Methods: 3-methylcholanthrene(MCA) and diethyinitrosamine(DEN) were used to induce lung squamous cell carcinoma by intra-left lobar-bronchial instillation in Wistar rats. The 80 rats (10 were in control group instilled with iodized oil) were sacrificed in turn from 15 days to 75 days after instillation. S-P method was used to determine the expressions of VEGF and FLK-1. Intertumor microvessel density(MVD) was marked by anti-von Willebrand factor monoantibody. Results: During carcinogenesis, the expressions of VEGF and FLK-1 were increased，MVD was also increased. Significant differences of MVD and VEGF expression were found in dysplasia, carcinoma in situ (CIS) and early-stage infiltration carcinoma respectively (P< 0.01). Significant difference were observed in FLK-1 expression(P< 0.05) between the CIS and the early-stage infiltration carcinoma. The VEGF expression was correlated with MVD (r=0.983 7,P< 0.01) and FLK-1 expression (r=0.968 8,P< 0.01),respecfively. The expression of FLK-1 was found in tumor cells, vascular endothelial cells, and vascular smooth musclaris cells, which was higher in tumor cells than those in other cells. Conclusions: Vasculature plays a role in lung carcinogenesis. VEGF and FLK-1 are highly related to angiogenesis and infiltration of tumor. VEGF plays a role in tumor vasculature and carcinogenesis in autocrine and paracine pathway.更多还原