【摘要】 目的探讨骨髓间充质干细胞(bone marrow mesenchymal stromal cells,BMSCs)侧脑室移植治疗血管性痴呆(vascular dementia,VaD)模型对大鼠行为学及海马钙调蛋白(calmodulin,CaM)、钙调蛋白依赖性激酶Ⅱ(calcium/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)表达的影响。方法以全骨髓贴壁法培养大鼠骨髓间充质干细胞(bone marrow mesenchymal stromal cells,BMSCs);流式细胞仪对所培养BMSCs进行表面抗原鉴定;成纤维生长因子(basic fibroblast growth factorbfic,b FGF)和丁羟基茴香醚(beta hydroxy acid,BHA)诱导BMSCs分化为神经元细胞,并对诱导后的细胞,进行神经元特异性的免疫组化鉴定;采用改良四血管法制备Va D模型,设立对照组,造模4 w后将VaD大鼠按随机数字表法分为对照组、模型组、BMSCs治疗组。观察4 w后实验大鼠的行为学表现及应用Real-time PCR检测海马CaM、CaMKⅡ表达水平。结果 BMSCs治疗组行为学表现有明显改善。其海马CaM、CaMKⅡmRNA表达比模型组降低(P<0.05)。结论侧脑室移植BMSCs显著改善VaD大鼠行为学表现,并使其海马CaM、CaMKⅡ表达降低。更多还原

【Abstract】 Objective To investigate the effects of bone marrow meseuchymal stromal cells( BMSCs) transplantation on behavioral performance,calmodulin( CaM) and calcium / calmodulin-dependent protein kinase Ⅱ( CaMKⅡ) expression in the hippocampus of vascular dementia( VaD) rats. Methods The BMSCs of rats were isolated and purified by the whole bone marrow adherence method. BMSCs differentiation into neuronal cells was induced by basic fibroblast growth factorbfic( bFGF) and beta hydroxy acid( BHA),Specific of neuron in the induced cells were identified by immunohistochemistry. The SD rats were randomized into the control group and model control group,the modified Pulsinelli’s four-vessel occlusion method was adopted in the model group to replicate Va D model. Four weeks after modeling,the VaD rats were divided randomly into three groups:( 1) control group;( 2) Va D modle group;( 3) BMSCs group. Morris water maze performance and CaM and CaMKⅡ expression in the hippocampus were observed at 4 weeks after transplantation. Results The moris water maze performance was significantly improved in mannitol with BMSCs group compared with VaD model group.The results showed that the CaM、CaMKⅡ mRNA and protein expression levels in the VaD model group were higher than that in the control group( P < 0. 05),compared with the VaD model group,CaM and CaMKⅡ expression were lowered in the stem cell treatment group( P < 0. 05). Conclusions Intracerebroventricular BMSCs transplantation improves the behavioral performance of VaD rats and decreases the CaM and CaMKⅡ expression in hippocampal of VaD rats.更多还原