神经生长因子纳米粒透过AD大鼠血脑屏障的实验研究

Study on transportation of nerve growth factor-polybutylcyanoacrylate-nanoparticles across blood-brain barriers of rat

目的:制备神经生长因子聚氰基丙烯酸丁酯(nerve growth factor-polybutylcyanoacrylate,NGF-PBCA)纳米粒并评价质量,探讨其在阿尔茨海默病(Alzheimer′sdisease,AD)大鼠体内透过血脑屏障的情况。方法:采用乳化聚合法制备NGF纳米粒并评价质量;Wistar大鼠30只,D-半乳糖和Aβ1-40先后注射实验组大鼠脑室后经Morris水迷宫法鉴定,制备有效AD大鼠模型;实验组静注NGF纳米粒后,Morris水迷宫法检测动物学习记忆能力的变化;ELISA法检测动物脑内NGF含量改变。结果:NGF-PBCA-纳米粒呈圆球形,包封率为83.56%,载药量为22.87%。与对照组相比,实验组动物找到平台时间明显下降,脑组织内NGF含量显著增加(P<0.01)。结论:乳化聚合法制备的NGF纳米粒,可使AD大鼠学习记忆能力损伤程度减轻,可增加外源性NGF通过AD大鼠血脑屏障的数量。

Objective To prepare and evaluate the nerve growth factor （NGF） - polybutylcyanoacrylate （PBCA）-nanoparticles, and to investigate its penetrability across blood-brain barriers of Alzheimer＇s disease （AD） rat. Methods NGF-PBCA-nanoparticles were prepared by emulsion polymerization method and using transmission electron microscope to observe nanopartiele morphology. The entrapment efficiency and loading efficiency of NGF- PBCA-nanopartieles were measured by means of UV spectra. 30 Wistar rats were injected D-galactose and Af31-40 then were detected through method of Morris water labyrinth to ensure they were effective AD models, After injected NGF-PBCA-nanoparticles, the learning and memory capabilities spatial of these AD rats were observed by Morris water labyrinth. The level of NGF in the brain of AD rat was measured by ELISA method. Results The NGF-PBCA- nanoparticles were uniform spheres with drug entrapment efficiency and loading efficiency 22.87% and 83.56%. Compare with the control, the times of experimental group to find the platform were depress remarkably, the level of NGF in the brain of AD rat was elevated expressly （P 〈 0.01 ）. Conclusion NGF-PBCA-nanoparticles obtained through emulsion polymerization method were uniform morphology bearing higher drug entrapment efficiency and loading efficiency. NGF-PBCA-nanoparticles could restrain the damage of the learning and memory capabilities spatial of AD rats, and could increase the penetrability across blood-brain barriers of AD rats.