论文部分内容阅读
目的探讨内皮抑素对胶质瘤病理特征的影响及分子药理学机制。方法利用经抗性筛选可表达内皮抑素的C6细胞裸鼠皮下注射制作胶质瘤模型,光镜和电镜观察其病理特征,ELISA法检测瘤组织中VEGF含量。结果转染有内皮抑素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(P<0.01)。前者肿瘤边界清楚,瘤体未见明显的出血和囊性变,瘤体和瘤周均无明显的水肿;瘤组织内血管稀少,未见类微血管样结构;瘤体内可见大片不规则坏死,但坏死灶周和瘤周均无明显的血管反应,瘤周侵袭少见,可见凋亡瘤细胞;血管内皮细胞胞质内未见内VVO样结构,基板不连续,基底膜疏松。而仅转染有空载体的C6胶质瘤瘤周血管反应明显,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,血管内皮细胞胞质内VVO样结构较多,水肿越明显VVO样结构越多见,并与移植瘤组织中VEGF表达相一致,血管基板完整、连续,多数基质疏松,呈多层排列,外层可见少量胶原纤维。所观察的几种肿瘤中的微血管内皮细胞孔窗及血管周胶原纤维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。结论内皮抑素不会直接诱导胶质瘤组织内血管内皮细胞的凋亡,但可通过诱导VEGF的表达的下调而抑制瘤周血管反应和肿瘤新血管的生成。
Objective To investigate the effect of endostatin on the pathological features of glioma and its molecular pharmacological mechanism. Methods The glioma model was established by subcutaneous injection of C6 cells transfected with endostatin. The pathological features were observed under light microscope and electron microscope. The content of VEGF in the tumor tissue was detected by ELISA. Results The content of VEGF in C6 glioma transfected with endostatin cDNA fragment was significantly lower than that in C6 glioma transfected with empty vector (P <0.01). The former had clear boundary of tumor, no significant hemorrhage and cystic change in the tumor, no obvious edema in the tumor and peritumoral neoplasm. There were few vessels in the tumor tissue and no microvascular-like structure. Large irregular necrosis appeared in the tumor, There was no obvious vascular reaction in necrotic lesions and peritumoral neoplasms, with rare tumor invasion and apoptotic tumor cells. VVO-like structure was not found in the cytoplasm of vascular endothelial cells, and the substrate was not continuous and the basement membrane was loose. However, only the glioma cells with empty vector transfected with obvious peripheral vascular reaction, tumor and peritumoral edema serious, tumor cells can invade the peritumoral tissue, tumor tissue was hemorrhagic necrosis, and the formation of tumor-like microvascular-like structure , VVO-like structure of the vascular endothelial cells more cytoplasm, the more obvious VVO-like edema-like structure, and with the VEGF expression in xenograft tumor tissue consistent, vascular substrate integrity, continuous, most of the matrix loose, were arranged in layers, Layer visible a small amount of collagen fibers. There were no significant relationships between the micro-vascular endothelial cell window and perivascular collagen in the observed tumors and the transfected target genes, and the apoptosis of endothelial cells was not obvious. Conclusion Endostatin can not directly induce the apoptosis of vascular endothelial cells in glioma tissue, but it can inhibit the development of perivascular vascular reaction and tumor neovascularization by inducing the down-regulation of VEGF expression.