hUC-MSCs和白藜芦醇对AD小鼠学习记忆能力及脑内SIRT1信号通路的影响*
Effects of hUC-MSCs and resveratrol on learning and memory capability and SIRT signaling pathway in brain tissue of AD mice

目的:探讨人脐带间充质干细胞(hUC-MSCs)移植联合白藜芦醇(RES)灌胃对AD小鼠学习记忆能力的影响及对脑内SIRT1信号通路的调控作用。方法:40只AD小鼠随机分为AD组、hUC-MSCs组、RES组、hUC-MSCs联合RES组(联合组),每组10只。干预8周后,用Morris水迷宫评估小鼠学习记忆能力; 取小鼠脑组织,采用免疫组化法检测Nestin的表达,TUNEL检测神经细胞凋亡,qRT-PCR检测神经营养因子BDNF、NGF和NT-3 mRNA的表达水平,Western blot法检测SIRT1、PCNA、P53、P21和P16的表达。结果:hUC-MSCs与RES均可使AD小鼠逃避潜伏期缩短,穿越平台次数增多,目的象限停留时间增加; 海马区再生细胞增多,凋亡细胞减少,BDNF、NGF和NT-3 mRNA表达水平升高,SIRT1和PCNA蛋白的表达增强,P53、P21、P16蛋白的表达减弱(P＜0.05)。 hUC-MSCs和RES联合对AD小鼠学习记忆能力、神经细胞再生、BDNF以及SIRT1蛋白的表达具有协同作用(P＜0.05)。结论:hUC-MSCs移植和RES灌胃可能通过调控脑内SIRT1信号通路共同促进AD小鼠学习记忆能力的改善。
Aim: To investigate the effects of human umbilical cord derived mesenchymal stem cells(hUC-MSCs)transplantation and resveratrol(RES)gavage on the cognition of AD mice and SIRT1 signaling pathway in brain tissue.Methods: Forty AD mice were randomly allocated into AD group, hUC-MSCs group, RES group and hUC-MSCs combined with RES group(combined group). Eight weeks after intervention, Morris water maze was employed to evaluate the learning and memory capability; the brain tissue was prepared, immunohistochemistry was used to detect the expression of Nestin, TUNEL was used to detect cell apoptosis, qRT-PCR was used to examine the expressions of neurotropic factors BDNF, NGF and NT-3 mRNA,and Western blot was used to examine the expressions of SIRT1, PCNA, P53, P21 and P16 protein.Results: hUC-MSCs and RES could improve learning and memory capability, as evidenced by shorter latency, more crosses and time spent in the target quadrant in the Morris water maze; hUC-MSCs and RES could both enhance hippocampus neurogenesis,alleviate apoptosis,upregulate the expressions of BDNF, NGF and NT-3 mRNA as well as enhance the expressions of SIRT1 and PCNA and inhibit the expressions of P53, P21 and P16. Furthermore, hUC-MSCs and RES exerted synergistic effects on the learning and memory capability,regeneration of neuronal cells as well as upregulated the expressions of BDNF and SIRT1.Conclusion: hUC-MSCs transplantation and RES gavage could synergistically improve learning and memory capability of AD mice via regulating SIRT1 signaling pathway