摘要
背景:研究发现脑源性神经营养因子(BDNF)修饰的人间充质干细胞可用于治疗脊髓损伤和创伤性脑损伤等,但对阿尔茨海默病是否有疗效,既往鲜有报道。目的:观察脑源性神经营养因子修饰人羊膜间充质干细胞(human amniotic mesenchymal stem cells,hAMSCs)对阿尔茨海默病大鼠学习记忆能力和海马胆碱乙酰转移酶、基底前脑神经生长因子表达的影响。方法:40只健康雄性成年SD大鼠随机分为对照组、模型组、hAMSCs组、BDNF-hAMSCs组,每组10只。采用双侧海马注射β-淀粉样蛋白25-35构建阿尔茨海默病模型,第14天后侧脑室注射10μL的hAMSCs或10μL的脑源性神经营养因子转染hAMSCs。移植后2周,采用Morris水迷宫测试评价大鼠学习记忆能力,免疫组化法检测海马胆碱乙酰转移酶的表达,RT-PCR检测基底前脑神经生长因子mRNA的表达。结果与结论:①Morris水迷宫测试第3,4,5天时,hAMSCs组和BDNF-hAMSCs组逃避潜伏期均低于模型组(P<0.05);测试第4,5天时,BDNF-hAMSCs组逃避潜伏期低于hAMSCs组(P<0.05);②模型组海马胆碱乙酰转移酶阳性神经元数、基底前脑神经生长因子表达量明显低于对照组(P<0.05);hAMSCs组和BDNF-hAMSCs组海马胆碱乙酰转移酶阳性神经元数、基底前脑神经生长因子表达量均高于模型组(P<0.05),并且BDNF-hAMSCs组高于hAMSCs组(P<0.05);③结果表明,用脑源性神经营养因子修饰hAMSCs可进一步提高hAMSCs治疗阿尔茨海默病的认知功能,并且可以明显提高海马胆碱乙酰转移酶和基底前脑神经生长因子的表达水平。
BACKGROUND:Studies have found that human mesenchymal stem cells modified by brain-derived neurotrophic factor(BDNF)can be used to treat spinal cord injury and traumatic brain injury,but whether there is a curative effect on Alzheimer’s disease is rare in the past reports.OBJECTIVE:To observe the effects of BDNF modified human amniotic mesenchymal stem cells(hAMSCs)on learning and memory ability and expression of choline acetyltransferase in hippocampus and nerve growth factor in basal forebrain of rats with Alzheimer’s disease.METHODS:Forty healthy male adult SD rats were randomly divided into control group,model group,hAMSCs group and BDNF-hAMSCs group with 10 rats in each group.Bilateral hippocampal injection ofβ-amyloid 25-35 was used to construct an Alzheimer’s disease model.On day 14,10μL of hAMSCs or 10μL of BDNF were injected into the posterior ventricle to transfect hAMSCs.At 2 weeks after transplantation,learning and memory abilities of rats were evaluated by Morris water maze test.Choline acetyltransferase expression in hippocampus was detected by immunohistochemistry.Nerve growth factor expression in the basal forebrain was detected by RT-PCR.RESULTS AND CONCLUSION:(1)At 3,4,and 5 days of Morris water maze test,the escape latencies of the hAMSCs group and the BDNF-hAMSCs group were lower than that in the model group(P<0.05).At 4 and 5 days,the escape latency of the BDNF-hAMSCs group was lower than that of the hAMSCs group(P<0.05).(2)The number of choline acetyltransferase positive neurons and nerve growth factor expression in the basal forebrain in hippocampus of model group were significantly lower than those of control group(P<0.05).The number of choline acetyltransferase positive neurons in the hippocampus and nerve growth factor expression in the basal forebrain of the hAMSCs group and the BDNF-hAMSCs group were higher than those of the model group(P<0.05),and the number of choline acetyltransferase positive neurons and nerve growth factor expression in the BDNF-hAMSCs group were higher th
作者
王玉香
崔传举
李彦玲
李艾帆
Wang Yuxiang;Cui Chuanju;Li Yanling;Li Aifan(Zhengzhou First People’s Hospital,Zhengzhou 450000,Henan Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2022年第13期2045-2049,共5页
Chinese Journal of Tissue Engineering Research
基金
河南省医学科技攻关计划联合共建项目(LHGJ20190983),项目负责人:李艾帆。
关键词
干细胞
人羊膜间充质干细胞
脑源性神经营养因子
阿尔茨海默病
胆碱乙酰转移酶
脑神经生长因子
认知功能
stem cells
human amniotic mesenchymal stem cells
brain-derived neurotrophic factor
alzheimer’s disease
choline acetyltransferase
brain nerve growth factor
cognitive function
