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目的比较定向移植输注转染外源性VEGF(血管内皮细胞生长因子)基因的成纤维细胞(VEGF-成纤维细胞)和原位注射rAAV(重组腺相关病毒)载体介导的VEGF基因对大鼠缺血性脑保护的疗效,从而寻找出适合临床的安全、有效的基因治疗方法。方法用线栓加环扎法建立SD大鼠大脑中动脉持续性闭塞(MCAO)模型。30只雄性SD大鼠随机分为假手术组、移植输注组、直接注射组、MCAO组和正常对照组。其中,移植输注组和直接注射组于术后24h内将VEGF-成纤维细胞和rAAV1-VEGF基因从大鼠脑缺血边缘区注入。结果移植VEGF-成纤维细胞和原位注射rAAV-VEGF基因均能减少脑梗死体积,且移植VEGF-成纤维细胞的作用明显优于原位注射基因,VEGF-成纤维细胞移植14d后大鼠脑内表达VEGF的阳性细胞数明显多于原位注射rAAV-VEGF治疗组。结论移植VEGF-成纤维细胞比原位注射rAAV-VEGF治疗基因对脑缺血更具保护作用。
OBJECTIVE: To compare the effect of VEGF-induced VEGF gene transfection on fibroblasts (VEGF-fibroblasts) transfected with exogenous VEGF (vascular endothelial growth factor) gene and rAAV (recombinant adeno-associated virus) Therapeutic efficacy of ischemic cerebral protection in rats, in order to find a suitable clinical safe and effective gene therapy. Methods The middle cerebral artery occlusion (MCAO) model of SD rats was established by using thread and cerclage method. Thirty male Sprague-Dawley rats were randomly divided into sham-operated group, transplanted group, direct injection group, MCAO group and normal control group. Among them, VEGF-fibroblasts and rAAV1-VEGF gene were transplanted into the marginal zone of cerebral ischemia in transplanted group and direct injection group within 24h after operation. Results Transplantation of VEGF-fibroblasts and rAAV-VEGF gene in situ reduced the volume of cerebral infarction, and the effect of transplanting VEGF-fibroblasts was better than that of in situ injection. After 14 days of transplantation of VEGF-fibroblasts, The number of positive cells expressing VEGF was significantly higher than that of rAAV-VEGF treated group. Conclusion Transplantation of VEGF-fibroblasts is more protective against cerebral ischemia than rAAV-VEGF treatment.