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

作　　者：王欣欣[1] 马珊珊[2] 孟楠[1] 邢衢 黄团结 程康[2] 杨波[1] 关方霞[1,2] WANG Xinxin MA Shanshan MENG Nanl X HUANG Tuanjie CHENG Kang YANG Bo GUAN Fangxia(Stem Cell Laboratory, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052 Stem Cell Laboratory, School of Life Sciences, Zhengzhou University, Zhengzhou 450001)

机构地区：[1]郑州大学第一附属医院干细胞研究室,郑州450052 [2]郑州大学生命科学院干细胞研究室,郑州450001

出　　处：《郑州大学学报（医学版）》2016年第5期576-579,共4页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金资助项目 81471306;U1404313;河南省高校科技创新团队支持计划 15IRTSTHN022;河南省科技创新人才计划 154200510008;河南省高等学校重点科研项目计划 17A310012;高等学校博士学科点专项科研基金资助课题 20114101110004

摘　　要：目的:探讨人脐带间充质干细胞(h UC-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、h UC-MSCs组、RES组、h UC-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:h UC-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-3mRNA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)。h UC-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:h UC-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.

关 键 词：白藜芦醇 人脐带间充质干细胞 阿尔茨海默症 SIRT1 小鼠 

分 类 号：R592[医药卫生—老年医学]