双功能融合蛋白RDP-BDNF对东莨菪碱所致认知功能障碍小鼠学习记忆的影响  

Effect of bifunctional RDP-BDNF fusion protein on ability of learning and memory of cognitive dysfunction mice induced by scopolamine

作　　者：张苗苗[1] 张恩齐[1] 高飞燕[1] 吴静[1] 项松涛[1] 付爱玲[1] 

机构地区：[1]西南大学药学院,重庆400716

出　　处：《中国药理学通报》2014年第11期1569-1574,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81273416);教育部回国人员启动基金[教外司留(2012)940号];新世纪优秀人才支持计划

摘　　要：目的研究融合蛋白RDP-BDNF穿越血脑屏障和神经保护活性的双重功能,为脑部疾病的治疗提供一种新方法。方法我们将新型穿膜肽狂犬病毒糖蛋白衍生肽(RDP)基因与BDNF基因融合并在大肠杆菌中表达,融合蛋白经尾静脉注射入小鼠体内,用ELISA法检测RDP-BDNF在脑和血清中的时效曲线;另外通过Morris水迷宫法研究融合蛋白对东莨菪碱所致的认知功能障碍小鼠学习记忆的影响,并探究其作用的机制。结果 RDP-BDNF可以穿过血脑屏障,且能提高东莨菪碱所致认知功能障碍小鼠的学习记忆能力。结论通过载体RDP介导实现蛋白质的入脑转运可能为脑部疾病的治疗提供一种新方法。Aim Through identification of the difunc-tionality of neuroprotection and passage of blood-brain barrier （ BBB） for RDP-BDNF fusion protein to offer a new strategy to treat brain diseases. Methods BDNF was conjugated to a novel cell penetrating peptide known as RDP which was derived from rabies virus gly-coprotein （ RVG） . The fusion protein RDP-BDNF was expressed in E. coli BL21 （ DE3 ） . After the intrave-nous injection of RDP-BDNF, the time effect curve of RDP-BDNF in the brains and serum was examined. Additionally , Morris water maze test was used to evalu-ate the effect of RDP-BDNF on scopolamine-induced amnesic mice, and the mechanism was also studied. Results RDP-BDNF could cross the BBB and exhibi-ted neuroprotective effects on the treatment of cognitive deficit induced by scopolamine in dementia model mice. Conclusions Delivery of protein therapeutics using RDP might offer a new and exciting strategy to treat brain diseases.

关 键 词：血脑屏障 水迷宫 认知障碍 胆碱能神经 穿膜肽 

分 类 号：R-332[医药卫生] R322.81