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 cer-clage 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 dl4 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 ofapoptosis 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.%目的 通过观察和比较单独或联合进行外源性血管内皮细胞生长因子(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24 h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14 d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.
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