裸小鼠异种移植人脑胶质瘤KDRmRNA的表达与血管形成的关系研究  

Kinase insert domain receptor （KDR） is associated with angiogenesis of xenografted human glioma in nude mice

作　　者：周格知[1] 袁坚列[1] 陈杰[1] 单国进[1] 章威[1] 冯一中[2] 兰青[3] 

机构地区：[1]金华市中心医院神经外科,321000 [2]苏州大学病理教研室 [3]苏州大学附属第二医院神经外科

出　　处：《浙江医学》2009年第6期745-747,750,共4页Zhejiang Medical Journal

摘　　要：目的探讨KDRmRNA在裸小鼠异种移植人脑胶质瘤不同生长阶段与不同组织区域中的表达规律，以及其与肿瘤血管形成的作用关系。方法利用恶性人脑胶质瘤细胞系SHG-44构建NC裸小鼠皮下移植瘤模型，30只荷瘤裸小鼠随机分成10组，每5d取一组肿瘤标本，移植瘤石蜡标本行H—E染色、KDRmRNA原位分子杂交和vWF免疫组化检测，光镜下检测上述基因的表达率和表达部位，并观察移植瘤中血管形成模式。同时仅用SHG-44细胞行原位杂交和免疫组化检测作为对照组。结果KDRmRNA表达于移植瘤中内皮细胞和部分瘤细胞，在瘤组织浸润边缘、瘤团中央、变性区域阳性细胞数较高。移植早期（5～15d）、中期（20～30d）和晚期（35—50d）的阳性细胞病理指数分别为26．4±2．1、169±18、247±2．2，中期显著低于早晚期（P〈0．01）。体外SHG-44细胞少量表达KDRmRNA。vWF标记的微血管密度平均计数为（31．53±9．06）个。移植瘤中存在内皮细胞被覆的血管、马赛克血管和肿瘤仿生血管三种血供模式。结论KDRmRNA在移植性人脑胶质瘤细胞中呈高表达，在不同的生长阶段和不同的瘤组织区域上存在差异表达的规律性，对肿瘤血管形成具有重要作用。KDR可作为抗胶质瘤血管形成的治疗靶点。Objective To investigate the association of KDR （kinase insert domain receptor） with angiogenesis of xenografted human glioma in nude mice. Methods Human glioma SHG-44 cells were transplanted in 30 nude mice, and 3 xenografted tumor samples were taken at an intervals of 5d. Hematoxylin eosin staining, in situ hybridization for KDR mRNA and immunohistochemical staining for vWF were performed in paraffin-embedded xenografted human glioma samples. In situ hybridization assay and immunohistochemical examination were also performed in cultured SHG-44 ceils. Results The expression of KDR mRNA was observed in most endothelial cells and some tumor cells in invasive regions, tumor nucleus and denatured regions. The pathological index of KDR mRNA positive cells was（ 26.4 ± 2.1 ）, （ 16.9 ±1.8 ）and（ 24.7 ± 2.2）, respectively in early period（5～15d）, intermediate period （20～30d）and later period （35～50d）. The KDR mRNA positive cells in intermediate period were less than those in early period and later period （P〈 0.01）. Expression of KDR mRNA in cultured SHG-44 cells was mild in vitro. The average micro-vascular density labeled by vWF was 31.53 ±9.06. Mosaic vasculature of tumor cells cooperating with endothelial cells, tumor cell-lined vasculature and endothelium-dependent vasculature were found in xenografted glioma. Conclusion Results indicate that KDR may play an important role in angiogenesis of xenografted human glioma.

关 键 词：胶质瘤 移植 血管形成 插入型激酶受体 马赛克血管 肿瘤仿生血管 

分 类 号：R737.31[医药卫生—肿瘤] R739.41[医药卫生—临床医学]