骨髓间充质干细胞移植对老年性痴呆大鼠学习和记忆能力的影响

Transplantation of bone marrow mesenchymal stem cells improves the ability of learning and memory of a rat model of Alzheimer's disease

【目的】本研究旨在探索骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)移植对老年性痴呆大鼠学习和记忆的影响。【方法】选用24月龄健康雄性Wistar大鼠制备自然衰老痴呆模型,将模型大鼠随机分为3组,每组10只。对照组大鼠双侧海马注射生理盐水;干细胞组大鼠注射BMSCs;分化组大鼠注射定向神经诱导的BMSCs。大鼠的学习能力在术前1 d及术后6周通过Y迷宫试验测定,记忆能力测定在学习能力测定48 h后进行;同时采用Morris水迷宫观察大鼠空间学习和记忆能力;采用免疫荧光组织化学染色法观察大鼠海马区胆碱乙酰化酶(choline acetyltransferase,ChAT)阳性细胞。【结果】对照组大鼠学习和记忆成绩均下降,与术前相比,差异无显著性意义(P>0.05);干细胞组大鼠学习和记忆成绩均提高,与移植前相比差异无显著性意义(P>0.05);分化组大鼠学习和记忆成绩均较移植前明显提高(P<0.01);与对照组相比,其他两组大鼠学习和记忆成绩均提高(P<0.05)。分化组大鼠逃避潜伏期较对照组明显缩短(P<0.01)。分化组大鼠海马区可观察到ChAT阳性细胞。【结论】BMSCs移植可改善老年性痴呆大鼠的学习和记忆能力,且定向神经诱导分化的BMSCs移植治疗效果优于未分化的BMSCs,提示BMSCs移植可能成为治疗痴呆大鼠认知功能障碍的一种方法。

[Objective]To evaluate the effect of bone marrow mesenchymal stem cell （BMSC） transplantation on the ability of learning and memory in Alzheimer＇ s disease （AD） rats. [Methods] The natural senile AD rat model was chosen from the healthy male Wistar rats aged 24 months. The AD rats were randomly divided into three groups with ten animals in each group. In the control group, rats were injected bilaterally with physiological saline into the hippocampus. In the BMSC group, rats received BMSCs. In the differentiation group, rats received injection of neuronal induced BMSCs. The learning ability of the AD rats was detected by Y type maze test one day before and 6 week after operation. The memory ability was tested 48 hours after learning test. The spatial learning and memory ability of rats was evaluated with Morris water maze. The expression localization of choline acetyltransferase （CHAT） in the hippocampus of ratsThe learning and memory scores decreased in control group and increased in BMSC transplantation group, there were all not statistics significance compared with that before transplant treatment （P 〉 0.05）, The learning and memory scores were higher than before in differentiation group （P 〈 0.01）. There was significant difference between control group and the other groups （P 〈 0.05）. The escape latency of hidden platform in differentiation group decreasedobviously as compared with control group （P 〈 0.01）. The ChAT-positive neurons were observed in the hippocampus of rats of the differentiation group. [ Conclusions ] BMSC transplantation may improve the learning and memory ability of AD rats. Neuronal induced BMSC transplantation is superior to undifferentiated BMSCs. Our results demonstrate that BMSCs can play an important role in treating cognitive disturbance of AD rats.