血管内皮生长因子基因转染骨髓间充质干细胞移植治疗放射性脑损伤认知功能损害

目的 探讨血管内皮生长因子(VEGF)基因转染同种异体骨髓间充质干细胞(MSCs)移植治疗对SD大鼠放射性脑损伤认知功能损害的影响.方法 体外分离、纯化、培养大鼠MSCs.构建VEGF腺病毒载体.单次40Gy全脑照射成年SD大鼠,制备脑损伤模型.大鼠随机分为未照射组、单纯照射组和细胞移植3组.细胞移植组采用经尾静脉注射转染后的MSCs.各组大鼠在照射后1个月、2个月、3个月、4个月和6个月分别进行Morris水迷宫试验,采用平均逃避潜伏期和搜索策略两个指标评价大鼠学习认知能力.血管内皮细胞标志物VIII因子免疫组化染色,评价脑微血管密度改变.结果 照射组在3个月时血管密度与未照射组相比明显下降(P<0.05),4个月时开始出现明显的认知功能下降,平均潜伏期(96.14±8.09)s]和搜索策略(15.03±1.76)%]差异有显著性(P<0.05).细胞移植组大鼠的学习认知能力显著增加,平均潜伏期(69.74±7.13)s]和搜索策略(23.74±1.51)%,与单纯照射组相比差异有显著性(P<0.05),在3个月和6个月时,脑微血管密度较单纯照射组显著增加(P<0.05).结论 VEGF基因转染骨髓间充质干细胞移植治疗能够促进放射后大鼠脑微血管的再生和改善其认知功能.

The treatment of mesenchymal stem cells transplantation combining with vascular endothelial growth factor gene can improve radiation cognitive impairment

ObjectiveTo study the treatment of mesenchymal stem cells (MSCs) transplantation combining with vascular endothelial growth factor gene on cognitive function of radiation brain injury. MethodsTo establish a method isolation,purification and cultivation of MSCs in vitro. To construct VEGF165 with adenovirus carrier. The brains of adult Sprague Dawley rats were irradiated with 40Gy in one single time.The irraditated rats were divided into two groups,one group were only irraditated,the other therapy group accepted transplantation. The infected MSCs were injected in rats through tail vein.Cognitive function was assessed using Morris maze.All groups rats were taken to Morris maze tests on every time point Average escape latency and search strategy were scaled and analyzed.Immunohistochemical assessment of the endothelial cell marker von Willebrand factor was vessel density. ResultsThe vessel density of irraditated rats decreased significantly on 3 months time point compared to control groups . Statistic differences of average escape latency and search strategy were found on 4 months(P<0.05). The Cognitive function of therapy groups were improved compared to groups who accepted no transplantation (P<0.05).On 3 months an 6 months time point, the vessel density of transplantation groups were improved compared to irraditated groups(P<0.05).ConclusionThe treatment of mesenchymal stem cells transplantation combining with vascular endothelial growth factor gene can improve radiation cognitive decline and capillary angiogenesis.