神经生长因子缓释微球植入后阿尔茨海默病模型鼠基底前脑神经生长因子受体阳性神经元的变化  

Changes in nerve growth factor receptor-positive neurons of the basal forebrain in rat Alzheimer's disease models after recombinant human nerve growth factor sustained release microspheres implantation

作　　者：谷海刚[1] 龙大宏[2] 宋存先[3] 李晓滨[1] 

机构地区：[1]广州医学院组织胚胎学教研室,广东省广州市510182 [2]广州医学院解剖学教研室,广东省广州市510182 [3]中国医学科学院北京协和医学院生物医学工程研究所,天津市300192

出　　处：《中国组织工程研究与临床康复》2009年第3期461-465,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家自然科学基金项目(30800345);广东省医学科研基金项目(B2008071);广州医学院基金项目(0706059)~~

摘　　要：背景:已有研究表明,神经营养因子对中枢和周围神经损伤后的存活修复有促进作用。然而,神经生长因子是大分子蛋白类物质,生物半衰期很短,很难透过血脑屏障,寻找有效的神经营养因子投递系统至关重要。目的:观察了神经生长因子微球对阿尔茨海默病模型鼠基底前脑神经生长因子受体阳性神经元的保护作用。设计、时间及地点:随机对照动物实验,于2005-11/2006-07在广州医学院神经生物学实验室完成。材料:采用双乳化技术制备神经生长因子缓释微球。28只SD大鼠,随机分为3组:正常对照组8只,模型对照组8只,神经生长因子缓释微球植入组12只。方法:模型对照组和神经生长因子缓释微球植入组左侧穹隆海马伞切断制备阿尔茨海默病模型,正常对照组不做任何处理。神经生长因子缓释微球植入组切断后即刻行基底前脑注射神经生长因子缓释微球。正常对照组和模型对照组注射等量生理盐水。主要观察指标:注射4周后,利用免疫组化法观察各组大鼠基底前脑神经生长因子受体阳性神经元变化。结果:28只大鼠均进入结果分析。模型对照组损伤侧的内侧隔核和斜角带核的神经生长因子受体阳性神经元大量减少,分别减少59.7%和54.4%;神经生长因子缓释微球植入组损伤侧的内侧隔核和斜角带核细胞数分别减少17.9%和19.8%,明显高于模型对照组损伤侧的神经生长因子受体阳性神经元存活数(P<0.05)。结论:神经生长因子缓释微球植入对阿尔茨海默病模型鼠基底前脑神经生长因子受体阳性神经元有明显的保护作用。BACKGROUND： Previous studies have confirmed that neurotrophic factor plays a role in recovery of central and peripheral nerve injury. However, nerve growth factor （NGF） is a kind of macromolecular protein substance. Its half life is short, and it is hard to pass through brain blood barrier. So it is very important to find out an effective neurotrophic factor delivery system. OBJECTIVE： To verify the protection of recombinant human NGF sustained release microspheres on the NGF receptor-positive neurons in the basal forebrain of the rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A randomized control animal study was performed in the Laboratory of Neurobiology, Guangzhou Medical College from December 2005 to July 2006. MATERIALS： Recombinant human NGF sustained release microspheres were prepared by a double emulsion technique. A total of 28 Sprague Dawley rats were randomly divided into three groups： normal control group （n =8）, model control group （n=8）, and implantation group （n =12）. METHODS： The Alzheimer＇s disease models were prepared in the model control and implantation groups by fornix-fimbria transaction in left lateral. There was no intervention in the control group. The recombinant human NGF sustained release microspheres were injected into the basal forebrain of rats in the implantation group at once after model establishment. The same volume of normal saline was injected into the basal forebrain of rats in the normal control and model control groups at the same time. MAIN OUTCOME MEASURES： At 4 weeks after injection, changes of NGF receptor-positive neurons in the basal forebrain of the rats in the three groups were observed by immunohistochemistry. RESULTS： All rats were enrolled in the final analysis. NGF receptor-positive neurons in the medial septum and diagonal band nucleus of rats in the model control group were greatly reduced, and the percentages of neurons were reduced by 59.7% and 54.4%, respectively. In the implantation group, the percentages o

关 键 词：阿尔茨海默病 神经生长因子微球 NGFR阳性神经元 基底前脑 大鼠 

分 类 号：R318[医药卫生—生物医学工程]