骨髓间充质干细胞移植对老年性痴呆大鼠空间学习记忆能力的影响

关键词：老年性痴呆  水迷宫  骨髓间充质干细胞  立体定向移植

Keywords:Alzheimer's disease  water maze  bone marrow mesenchymal stem cells  stereotypical transplantation

摘要：

      摘要 目的:研究骨髓间充质干细胞（BMSCs）移植对淀粉样蛋白-β1-40(Aβ1-40)诱导的老年性痴呆 (Alzheimer's disease, AD )模型大鼠行为学的影响，并探讨其治疗AD的可能机制。 方法:采用向大鼠双侧海马立体定向注射Aβ1-40诱导AD动物模型，造模后3周采用同样方法移植骨髓间充质干细胞，采用Morris水迷宫观察大鼠行为学变化。造模后2个月处死大鼠，观察海马组织有无溴脱氧尿嘧啶核苷（BrdU）+神经元特异性烯醇化酶(NSE)、BrdU+胶质纤维酸性蛋白（GFAP）免疫组织化学双染阳性细胞，并且观察从侧脑室到海马是否存在神经元前体细胞（NPs）的标志——双皮素(DCX)的吻侧迁移流。 结果:模型组大鼠逃避潜伏期较对照组明显延长，移植治疗组大鼠逃避潜伏期较模型组缩短。移植组大鼠海马组织及其周围可见免疫组织化学双染阳性细胞，但未见从侧脑室到海马关于DCX的吻侧迁移流。 结论: BMSCs移植能够改善AD大鼠空间学习记忆能力，提示BMSCs移植可能成为治疗AD大鼠的一种方法。

Abstract:

      Abstract Objective: To study the effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) on learning and memory ability and its mechanism in rats with Alzheimer's disease induced by amyloid-β1-40 (Aβ1-40) injection. Method: AD model was induced by injecting Aβ1-40 into bilateral hippocampus. Three weeks later, the bone marrow mesenchymal stem cells was implanted. The learning and memory abilities of rats were evaluated with Morris water maze.Rats were sacrificed after 2 months. Bromodeoxyuridine(BrdU)+neuron specific enolase(NSE), BrdU+glial fibrillary acidic protein (GFAP) immunohistochemistry double-staining cells, and the migration of doublecortin (DCX, the neuron precursors marker) from subventricular zone to the damaged hippocampus were observed. Result:The escape latency of hidden platform in AD group delayed significantly(P<0.05),the escape latency in transplantation treatment group decreased obviously as compared with model group(P<0.05). The immunohistochemistry double-staining cells could be found at the center of damaged site(bilateral hippocampus) and the surrounding sites in rats of transplantation group, the migration of doublecortin from subventricular zone to the damaged hippocampus wasn't observed. Conclusion：The implantation of BMSCs maybe have the effect of improving spacial learning-dysmnesia of AD rats.