摘要
目的:探讨脑纹状体内植入环磷酸腺苷反应元件结合蛋白(CREB)基因修饰的骨髓间充质干细胞(BMSCs)对帕金森病(PD)大鼠学习记忆能力影响。方法:向36只Wistar大鼠脑纹状体内注射6-羟基多巴胺(6-OHDA)制备PD大鼠模型,造模后第2周腹腔注射阿扑吗啡(APO)诱导转圈,30 min内每分钟旋转超过7圈即为造模成功。选取造模成功的大鼠30只,随机分为PBS注射组、BMSCs移植组、CREB-BMSCs移植组,各组大鼠分别注射10μl PBS、BMSCs、CREB基因修饰的BMSCs(CREB-BMSCs),移植2周、5周、8周后,腹腔注射APO诱导大鼠转圈,记录并比较各组大鼠旋转圈数,采用Morris水迷宫实验检测移植后PD大鼠学习记忆能力,采用Western blot法检测移植后PD大鼠脑纹状体内p-CREB蛋白水平。结果:移植2周、5周、8周后,BMSCs移植组PD大鼠旋转圈数明显低于PBS注射组(P<0.05),CREB-BMSCs移植组PD大鼠旋转圈数明显低于BMSCs移植组(P<0.05);BMSCs移植组PD大鼠在Morris水迷宫目标象限内的停留时间明显多于PBS注射组(P<0.05),CREB-BMSCs移植组PD大鼠在Morris水迷宫目标象限内的停留时间明显多于BMSCs移植组(P<0.05);BMSCs移植组PD大鼠p-CREB蛋白水平明显高于PBS注射组(P<0.05),CREB-BMSCs移植组PD大鼠p-CREB蛋白水平明显高于BMSCs移植组(P<0.05)。结论:脑纹状体内植入CREB基因修饰的BMSCs可有效改善帕金森大鼠学习记忆能力。
Objective:To investigate the effect of intrastriatal implantation of cAMP response element binding protein(CREB) gene-modified bone marrow derived mesenchymal stem cells(BMSCs) on the learning-memory ability in rats of Parkinson′s disease(PD) models.Methods: 36 Wistar rats were used to prepare PD models,the rats were induced to rotate by injecting apomorphine(APO) while 2 weeks after operation, and the number of rotations for the successful PD model rats was greater than 7 r/min, so only 30 of them were successfully established,which were divided into three groups,PBS injection group,BMSCs transplantation group and CREB-BMSCs transplantation group.Rats in each group were injected with 10 μl PBS,BMSCs and CREB-BMSCs respectively.After 2,5 and 8 weeks of transplantation,rats underwent the rotation test evoked by the APO and Morris water maze test,then the Western blot was used to detect the level of p-CREB protein in the striatum of PD rats after transplantation.Results: After 2,5 and 8 weeks of transplantation,the decrement of the APO-induced rotation was most obvious in the CREB-BMSCs transplantation group,followed by the BMSCs transplantation group and PBS injection group,with statistic difference(P<0.05).The retention time of PD rats in Morris water maze target quadrant was longest in the CREB-BMSCs transplantation group,followed by the BMSCs transplantation group and PBS injection group,with statistic difference(P<0.05).The level of p-CREB protein in the striatum of PD rats was highest in the CREB-BMSCs transplantation group,followed by the BMSCs transplantation group and PBS injection group,with statistic difference(P<0.05).Conclusion: Intrastriatal implantation of CREB gene-modified BMSCs can effectively ameliorate the learning-memory ability in rats of PD models.
作者
余恒
宋光捷
YU Heng;SONG Guang-Jie(Neurology Department of North Hospital District Xiangyang Center Hospital,Affiliated Hospital of Hubei University of Arts and Sciences,Xiangyang 441003,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2020年第10期1180-1184,共5页
Chinese Journal of Immunology
基金
湖北省自然科学基金资助项目(2013CCV064)。
