rhMG53蛋白联合hUC-MSCs移植对阿尔茨海默鼠的治疗作用  

Therapeutic effects of rhMG53 combination with h UC-MSCs transplantation on Alzheimer's disease mice

作　　者：宋及时 马珊珊[1] 孟楠[2] 王欣欣[2] 姚宁 朱相展 程康[1] 杨波[2] 关方霞[1,2] 

机构地区：[1]郑州大学生命科学学院干细胞研究室,郑州450001 [2]郑州大学第一附属医院干细胞研究室,郑州450052 [3]中美(河南)荷美尔肿瘤研究院,郑州450000

出　　处：《郑州大学学报（医学版）》2016年第4期442-446,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金资助项目81471306;U1404313;河南省科技创新人才计划154200510008;河南省高校科技创新团队支持计划15IRTSTHN022;河南省产学研合作项目142107000008

摘　　要：目的:研究rh MG53蛋白联合人脐带间充质干细胞(h UC-MSCs)移植对阿尔茨海默模型鼠(APP转基因小鼠)的治疗作用。方法:40只APP+小鼠随机分为APP+组、h UC-MSCs组、rh MG53组和rh MG53联合h UC-MSCs组(联合组),分组处理1周后采用免疫组化法检测小鼠脑内h UC-MSCs的迁移率,3周后采用Morris水迷宫测试各组小鼠的学习和记忆能力,同时检测小鼠血清中SOD的活性和MDA的含量,并采用qRT-PCR和Western blot检测小鼠脑组织中衰老相关基因(sirt2、p CNA、p16、p53)的表达。结果:APP+组和rh MG53组未见h UC-MSCs迁移,h UCMSCs组和联合组存在h UC-MSCs迁移,且联合组迁移细胞更多(P<0.05)。h UC-MSCs移植可以使APP+小鼠的逃避潜伏期缩短,穿越平台次数增加以及平台所在象限停留时间增加(P<0.05);h UC-MSCs移植和rh MG53均可使APP+小鼠血清SOD活性增加,MDA含量下降,且二者联用对MDA的影响有协同作用(P<0.05);h UC-MSCs移植和rh MG53均可使APP+小鼠脑组织sirt2和p CNA mRNA和蛋白的相对表达量升高,且二者联用对多数衰老相关基因表达的影响有交互作用(P<0.05)。结论:外源rh MG53蛋白可以提高小鼠脑内h UC-MSCs的迁移,促进h UCMSCs对阿尔茨海默鼠的治疗作用。Aim： To research the effects of rh MG53 combination with h UC-MSCs transplantation on Alzheimer＇ s disease mice. Methods： Forty APP＋mice were randomly allocated into four groups： APP＋group,h UC-MSCs group,rhMG53 group and rh MG53 combined with h UC-MSCs group. The migration of h UC-MSCs was quantified by immunohistochemistry at one week after transplantation. And the learning and memory ability was measured by Morris water maze test at three weeks after transplantation. The activity of superoxide dismutase（ SOD） and the concentration of malonaldehyde（ MDA） in the serum were also quantified. qRT-PCR and Western blot were used to detect the expressions of senescence related factors（ sirt2,p CNA,p16,p53）. Results： No migration of h UC-MSCs was found in APP＋group or rh MG53 group,while it was observed in the h UC-MSCs group and the combined group,and the amount of migration cells was higher in the combined group（ P 0. 05）. h UC-MSCs transplantation decreased the escaping latency,increased the times of crossing platform and the time spent in the platform quadrant（ P 0. 05）. h UC-MSCs transplantation and rh MG53 could both increase the activity of SOD and decrease the content of MDA in the serum of APP＋mice,and rh MG53 combined with h UCMSCs transplantation had synergistic effect on MDA（ P 0. 05）. h UC-MSCs transplantation and rh MG53 could both increase the expressions of sirt2 and p CNA mRNA and protein in the brain tissue of APP＋mice,and rh MG53 combined with h UC-MSCs transplantation had synergistic effect on the expression of most aging genes（ P 0. 05）. Conclusion： rh MG53 can improve the migration of h UC-MSCs in brain tissue of APP＋mice,and promote the therapeutic effect of h UC-MSCs on APP＋mice.

关 键 词：rhMG53 阿尔茨海默病 间充质干细胞 干细胞移植 小鼠 

分 类 号：R592[医药卫生—老年医学]