大鼠小脑脑脊液自体输入减少其大脑皮层和海马区的Aβ沉积  

Decreased Aβ deposition in cerebral cortex and hippocampus by auto-infusion of cerebrospinal fluid with metabolites from cerebellar neurons in rat

作　　者：陈魁[1,2] 杜婧[2] 徐峰[2] 王钊[2] 范丽[1,3] 

机构地区：[1]安徽医科大学药理学教研室,合肥230032 [2]清华大学医学院药物研究所,北京100084 [3]Division of Neuroscience,Oregon National Primate Research Center,Oregon Health&Science University

出　　处：《安徽医科大学学报》2010年第4期463-466,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:No.30572341);国家重点基础研究发展规划973计划资助项目(编号:2007CB507406);清华-裕元医学科学研究基金(编号:THYY20070008)

摘　　要：目的探讨大鼠小脑脑脊液自体输入对其大脑皮层和海马区β淀粉样蛋白(Aβ)含量的影响及作用机制。方法脑立体定位仪第四脑室抽取脑脊液并注射到同一只大鼠的侧脑室内,饲养1周后,断头法处死大鼠取海马及皮层组织,通过免疫组织化学和酶联免疫吸附试验检测大鼠大脑皮层和海马区Aβ含量,并用Western blot的方法检测胰岛素降解酶(IDE)的表达情况。结果实验组大鼠小脑脑脊液自体输入可以减少自体大脑皮层和海马区Aβ含量,包括可溶性Aβ(P<0.05)和不可溶性Aβ(P<0.05)的含量。同时,IDE的表达较对照组明显增加(P<0.05)。结论大鼠小脑脑脊液自体输入可以降低自体大脑皮层和海马区内的Aβ含量及其造成的病理损伤,这种作用可能是通过上调IDE的表达来实现的。该研究为阿尔茨海默病的临床治疗提供了一个新思路。Objective To investigate the effect and the underlying mechanisms of auto-infusion of cerebrospinal fluid on the deposition of beta-amyloid（Aβ）in cerebral cortex and hippocampus in rat.Methods Cerebrospinal fluid was drawn from the fourth ventricle and then was injected into the lateral ventricle of the same rat,guided by stereotaxic apparatus.Contents,as well as the deposition of Aβ in cerebral cortex and hippocampus were determined by enzyme linked immunosorbent assay（ELISA） and immunohistochemistry techniques.Western blot was also detected insulin degrading enzyme （IDE） expression in cerebral cortex.Results Auto-infusion of cerebrospinal fluid from the fourth ventricle could reduce the deposition of both soluble and insoluble Aβ in cerebral cortex and hippocampus in rat.Meanwhile,the expression of IDE which mediated the proteolysis of extracellular Aβ was up-regulated simultaneously in cerebral cortex. Conclusion Auto-infusion of cerebellar cerebrospinal fluid can inhibit the abnormal deposition of Aβ in cerebral cortex and hippocampus through up-regulating the expression of IDE.This study may bring a new insight to the possible treatment of Alzheimer′s disease.

关 键 词：阿尔茨海默病 海马 大脑皮质 淀粉样Β蛋白 

分 类 号：R745.7[医药卫生—神经病学与精神病学] R322.811[医药卫生—临床医学]