【摘要】 目的了解血管内皮细胞生长因子（VEGF）对胶质瘤病理形态的影响。方法利用光镜和电镜观察转染有反义VEGF cDNA片段的C₆胶质瘤细胞的裸鼠移植瘤的病理特征,ELISA法检测肿瘤组织中VEGF的含量。结果转染有反义VEGF cDNA片段的C₆胶质瘤组织中VEGF含量明显低于仅转染有空载体的C₆胶质瘤组织（P＜0．05）。前者瘤组织表面存在类包膜,瘤周血管反应轻。无明显瘤周水肿,瘤周侵袭少见,凋亡瘤细胞明显增多；血管内皮细胞胞浆内VVO样结构少见,基板不连续、单层,外周见胶原纤维；但个别肿瘤大者瘤组织中VEGF含量也高,且内皮细胞VVO样结构也随之增多。而后者瘤周血管反应明显,瘤体和瘤周水肿严重,瘤细胞可侵袭瘤周组织,瘤内组织明显出血坏死,且可见瘤细胞形成类微血管样结构,血管内皮细胞胞浆内VVO样结构较多,水肿越明显VVO样结构越多见,并与组织中VEGF含量相一致；基板较完整连续,多数基质疏松,呈多层排列,外层见少量胶原纤维。所观察的几种肿瘤中的微血管内皮细胞孔窗及内皮细胞裂隙与转染的目的基因无明显的关系,且内皮细胞的凋亡均不明显。结论胶质瘤细胞上VEGF表达的下调可促进胶质瘤细胞凋亡；VEGF通过内皮细胞内的VVO样结构增多引起血管渗透性增加致瘤体和瘤周水肿,而与内皮细胞上孔窗无明显的关系：胶质瘤组织中的血管基板完整连续与否与VEGF有关。更多还原

【Abstract】 Objective To investigate the influence of vascular endothelial cell growth factor （VEGF）on pathological morphology of C₆ glioma.Methods The C₆ cells,the C₆ clone stably transfected with antisense VEGF cDNA（AS-VEGF-C₆）and the C₆ clone stably transfected with empty vector pBudCE4.1 cDNA（pBud-C₆）were injected subcutaneously into nude mice to establish different tumor models respectively.The morphologic features of these tumor tissues were observed and compared with each other under light and electron microscopes;the expression of VEGF in tumor tissue was determined by ELISA.Results The expression of VEGF in AS-VEGF-C₆ glioma（AS-VEGF-C₆G） tissues was lower than that in C₆ glioma（C₆G）and pBud-C₆ glioma（pBud-C₆G）（P＜0.05）.Moreover, AS-VEGF-C₆G tissue was characteristic of a mimetic envelope,mild peritumoral vascular reaction and edema,rare invasion,and dramatically increased apoptosis of tumor cells,the basal lamina surrounded by collagen fibers were monolayer and discontinued,few vesicular vacuolar organelle（VVO）structure was observed in plasma of endothelial cells,interestingly though not frequently,increased VVO structure,as well as high VEGF expression,were detected in sample from large tumor mass.In C₆G and pBud-C₆G,tumor lesions were demonstrated to have a significant vascular reaction,intratumoral bleeding and necrosis,edema in and around tumor,and obvious surrounding infiltration;tumor cells formed structures like capillary vessel; under an electron microscope,plenty of WO structures were observed in plasma of endothelial cells;the worse the edema was,the more the VVO were,which coincided with the expression of VEGF;the mostly, loose basal lamina surrounded by small amounts of collagen fibers were multilayer and integrated and continuous.No correlation between gene transfection and fenestra formation or cleft of capillary endothelial cells was observed,and no apoptosis of endothelial cells was found.Conclusion The apoptosis of tumor cells was induced by the down-regulation of the expression of VEGF in C₆ glioma cells.The edema in and around tumor may directly resulted from the increased permeability of blood capillary due to more VVO structures induced by VEGF,having no obvious link with fenestration of capillary endothelial cells.In tumor tissue,VEGF played a critical role in the integrity and continuity of basal lamina of vessel.更多还原