【摘要】 目的探讨骨髓间充质干细胞(BMSCs)移植治疗对老年性痴呆(AD)大鼠中枢胆碱能系统的保护作用及机制。方法雄性Wistar大鼠45只,采用随机数字法分为双侧穹隆海马伞(FF)切断模型组(模型组,复制AD模型),假手术对照组(SOC组,除不切断双侧FF以外,其他操作同模型组),骨髓间充质干细胞(BMSCs)移植治疗组(BMSCs组,在模型制作成功2周后,每只大鼠接受1×106个BMSCs治疗)。采用免疫组化法检测海马胆碱能神经纤维胆碱乙酰转移酶(ChAT)的表达,RT-PCR检测基底前脑神经生长因子(NGF)mRNA表达。结果模型组在FF切断术后6周,其海马ChAT阳性神经纤维的积分光密度值(1249.71±143.25)明显低于SOC组(2059.58±166.69,P<0.05),BMSCs组(1807.02±133.85)与模型组相比,ChAT阳性纤维数量增多(P<0.05)。模型组基底前脑神经元NGFmRNA表达水平(0.45±0.08)与SOC组(1.14±0.12)比较明显降低(P<0.05),BMSCs组(0.78±0.09)较模型组有所升高(P<0.05)。结论BMSCs移植治疗对AD模型大鼠中枢胆碱能系统有保护作用,其机制可能与BMSCs移植上调基底前脑神经元NGF的表达有关。更多还原

【Abstract】 Objective To explore the protective effects and mechanism of transplantation of bone marrow mesenchymal stem cells(BMSCs) on central cholinergic system of rats with Alzheimer disease(AD).Methods Forty-five male Wistar rats were randomized into 3 groups(15 each) by using a random number table:fimbria-fornix(FF) transected model group(model group:AD model was established by bilateral hippocampal fimbria-fornix transection);sham group(SOC group:all the procedures but transection were the same as the model group);BMSCs transplantation group(BMSCs group:each rat was administered with 1×106 cells 2 weeks after AD model successfully established).Immunohistochemical assay and RT-PCR were used to detect the expression of choline acetyl transferase(ChAT) and mRNA expression of nerve growth factor(NGF) in the basal forebrain,respectively.Results In the 6th week after FF transection,the integral optical density value of ChAT expression was significatly lower in model group(1 249.71±143.25) than in SOC group(2 059.58±166.69,P<0.05),and also in BMSCs group(1 807.02±133.85,P<0.05).The mRNA expression was significantly lower in model group(0.45±0.08) than in SOC group(1.14±0.12,P<0.05),and also in BMSCs group(0.78±0.09,P<0.05).Conclusion BMSCs transplantation may have a protective effect on central cholinergic system in rats with AD,and NGF expression in basal forebrain may play a role in this effect.更多还原