外源性VEGF和bFGF基因治疗大鼠脑缺血疗效的比较研究  

VEGF and bFGF gene therapy for cerebral ischemia in rats

作　　者：邵林华[1] 孙青芳[2] 卞留贯[2] 陈亦华[1] 程振宇[1] 郑龙[1] 俞建华[1] 张晨冉[2] 顾吕伟[2] 

机构地区：[1]金华市人民医院,321000 [2]上海瑞金医院

出　　处：《浙江医学》2011年第11期1593-1595,共3页Zhejiang Medical Journal

基　　金：浙江省卫生厅科研计划资助项目（20078221）;金华市科技局科研计划资助项目（2007-03-044）

摘　　要：目的通过观察和比较单独或联合进行外源性血管r8皮细胞生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）基因治疗大鼠局灶性脑缺血的疗效，从而寻找出安全有效的基因治疗方法。方法用线栓加环扎方法建立SD大鼠大脑中动脉持续性闭塞（MCAO）模型。36只大鼠模型随机分为正常对照组、假手术组、VEGF基因治疗组、bFGF基因治疗组、基因联合治疗组和MCAO组，治疗组于术后24h内将分别表达VEGF和bFGF基因的重组腺相关病毒（rAAV）载体rAAV—VEGF和rAAV—bFGF通过大鼠侧脑室输注。术后14d取脑，用脱氧核苷酸末端转移酶介导的缺口末端标记法检测脑缺血边缘区脑细胞凋亡数，HE染色观察脑组织坏死情况。结果与MCAO组比较，VEGF基因治疗组、bFGF基因治疗组、基因联合治疗组脑缺血边缘区脑细胞凋亡数明显减少（P〈0．05），脑组织坏死体积缩小（P〈0．05），其中以基因联合治疗组更为显著。结论外源性VEGF和bFGF基因联合比VEGF或bFGF基因单独治疗大鼠脑缺血的效果更优。Objective To evaluate VEGF and bFGF gene therapy for cerebral ischemia in rats. Methods The cerebral ischemia model was established by permanent occlusion of middle cerebral artery（MCAO） with nylon suture embolization and cerclage in rats. The recombinant adeno-associated virus mediated vascular endothelial growth factor gene （rAAV-VEGF） and/or recombinant adeno-associated virus mediated basic fibroblast growth factor（rAAV-bFGF） were injected through the lateral cerebral ventricle within 24h after MCAO. On the d14 after the rAAV-VEGF and rAAV-bFGF injection,the rats were sacrificed and brain samples were taken for study. Results From observing the positive cells stained by terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） in the ischemic penumbra and analyzing the size of infarct by TTC staining,it was found that a significant reduction in the ratio of apoptosis cells and infarct volume was observed in the therapeutic groups when compared to the MCAO and sham-operated group（P〈0.05）, and it was more prominent in the therapeutic group by two genes combined therapy than by rAAV-VEGF or rAAV-bFGF alone（P〈0.05）. Conclusion Our results indicate that the VEGF together with bFGF gene therapy of the ischemic cerebrovascular diseases is a safe and effective gene transferring approach that may be suitable for clinical application.

关 键 词：脑缺血 血管内皮细胞生长因子 碱性成纤维细胞生长因子 脑室途径 基因治疗 大鼠 

分 类 号：R737.31[医药卫生—肿瘤]