骨髓间充质干细胞移植对阿尔茨海默病大鼠行为学的影响

Effects of bone marrow mesenchymal stem cell transplantation on ethology of rats with Alzheimer's disease

背景:目前研究表明,骨髓间充质干细胞作为包括阿尔茨海默病在内的神经退行性疾病的细胞替代治疗,可能是一种有应用前景的工程细胞,但其对阿尔茨海默病的治疗效果尚不明确。目的:观察定向诱导骨髓间充质干细胞移植对阿尔茨海默病大鼠行为学的影响,试图发现有效治疗阿尔茨海默病的策略。设计、时间及地点:随机对照动物实验,于2009-03在武警医学院生理学与病理生理学教研室完成。材料:健康雄性Wistar大鼠40只,鼠龄24个月,体质量450g左右。方法:自然衰老痴呆模型大鼠是通过迷宫试验筛选,将大鼠随机数字表法分为4组,每组10只。对照组大鼠双侧海马注射生理盐水;骨髓间充质干细胞移植组大鼠注射骨髓间充质干细胞;常氧分化移植组大鼠注射常氧环境下向神经元样细胞诱导的骨髓间充质干细胞;低氧分化移植组大鼠注射低氧环境下向神经元样细诱导的骨髓间充质干细胞。主要观察指标:阿尔茨海默病大鼠的学习和记忆能力在移植前及实验后8周通过Y迷宫试验测定,记忆能力测定在学习能力测定48h后进行。结果:对照组阿尔茨海默病大鼠术后学习记忆成绩均下降,与术前相比,差异无显著性意义(P>0.05);骨髓间充质干细胞移植组大鼠学习记忆成绩提高,与移植前相比差异无显著性意义(P>0.05);常氧分化移植组和低氧分化移植组大鼠学习记忆成绩均较移植前提高;与对照组相比,其他3组大鼠学习记忆成绩均提高(P<0.01)。结论:骨髓间充质干细胞移植可以改善阿尔茨海默病模型大鼠的学习记忆能力,提示骨髓间充质干细胞移植对痴呆大鼠的认知功能障碍有治疗作用,且定向诱导分化的骨髓间充质干细胞移植治疗优于未分化的骨髓间充质干细胞,低氧诱导分化的骨髓间充质干细胞移植治疗效果最佳。

BACKGROUND：Previous studies have shown that bone marrow mesenchymal stem cells （BMSCs） may be a promising candidate for cell-replacement therapies for neurodegenerative diseases including Alzheimer＇s disease （AD）.But,it is still unclear whether BMSCs have therapeutic effects on AD.OBJECTIVE：To investigate the influence of BMSC transplantation on ethology of rats with AD,and to find a potential strategy for the development of effective therapies for the treatment of AD.DESIGN,TIME AND SETTING：The randomized controlled study was performed at the Laboratory of the Department of Physiology and Pathophysiology,Medical College of Chinese People＇s Armed Police Force in March 2009.MATERIALS：A total of 40 healthy male Wistar rats aged 24 months were used in this study,weighing approximately 450 g.METHODS：The natural senile AD rat model was chosen by maze test.The AD rats were randomly divided into four groups with ten animals in each group.In the control group,rats were injected bilaterally with physiological saline into the hippocampus.In the BMSC transplantation group,rats received BMSCs.In the normoxic differentiation and transplantation group,rats received injection of BMSCs induced from neuron-like cells under normoxic condition.In the hypoxic differentiation and transplantation group,rats received injection of BMSCs induced from neuron-like cells under hypoxic condition.MAIN OUTCOME MEASURES：The learning and memory ability of the AD rats were detected by Y type maze test 8 weeks later.Memory ability was tested 48 hours after learning test.RESULTS：The 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 all higher than before in normoxic differentiation and transplantation group and hypoxic differentiation and transplantation group.There was significant difference between control group and the other groups （P〈0.01）.CONCLUSION：BMSC transplantation may improve the learning and memory ability of AD rats.Our results demonstrate that BMSCs not only play an important role in improving cognitive disturbance of AD rats.Oriented differentiated BMSC transplantation was superior to non-differentiated BMSCs.Transplantation of hypoxic differentiated BMSCs has obtained optimal outcomes.