重组腺伴随病毒载体表达hBDNF对大鼠基底前脑胆碱能神经元损伤的保护作用  

Protective effect of rAAV vector mediated hBDNF on rat basal forebrain cholinergic neurons damaged by amyloid β-peptide

作　　者：马东亮[1] 胡海涛[1] 杨蓬勃[1] 靳辉[1] 任惠民[1] 刘勇[1] 

机构地区：[1]西安交通大学医学院人体解剖学教研室,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2004年第1期27-29,47,共4页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：美国中华医学会基金资助 (CMB :82 4 1 3)

摘　　要：目的　探讨重组腺伴随病毒载体表达人脑源性神经营养因子 (hBDNF)对大鼠基底前脑胆碱能神经元损伤的保护作用。方法　用 β淀粉样肽 (Aβ2 5 3 5)注入大鼠Meynert核损伤胆碱能神经元。损伤后 8～ 10d行hBDNF重组腺伴随病毒脑内注射。经避暗回避试验测试大鼠学习记忆能力 ,组织学及免疫组织化学观察hBDNF表达以及胆碱能神经元数量变化。结果　避暗回避试验结果显示 ,应用hBDNF重组腺伴随病毒 4周后 ,实验组动物的学习记忆能力增强 ,行为明显改善。胆碱乙酰转移酶 (ChAT)免疫组织化学染色显示 ,注射点附近免疫反应阳性神经元散在或成群分布 ,数目明显增多 ,经与模型组比较 ,胆碱能神经元数量增高约 3 7%。结论　hBDNF重组腺伴随病毒可在脑内表达hBDNF ,表达的hBDNF对损伤的胆碱能神经元具有营养和保护作用。Objective To study the protective effect of recom binant adeno-associated virus (rAAV) vector mediated human brain-derived neuro trophic factor (hBDNF) on rat basal forebrain cholinergic neurons damaged by amy loid β -peptide (A β ). Methods A β 25-35 was injected into Meynert nucleus in order to damage cholinergic neurons. The hBDNF recombinant adeno-associated vi rus was injected in rat basal forebrain after 8～10 days. The learning and memor y ability was tested by passive avoidance and active avoidance. The hBDNF expres sion and number of cholinergic neurons were detected by histology and immunohist ochemistry. Results The results of passive and active avoidance showed that the learning and memory ability and behavior were significantly improved in the rats of experimental group after using rAAV-hBDNF. Choline acetyltransfera se (ChAT) immunoreactive neurons of the rAAV-hBDNF injection site increased and distributed in dispersion or in-group after 4w. The number of cholinergic neur ons of experimental group was increased by approximately 37% over that of the mo del group. Conclusion In the brain, rAAV-hBDNF can express hBDNF that can protect the damaged cholinergic neurons.

关 键 词：重组腺伴随病毒载体 HBDNF 大鼠 基底前脑 胆碱能神经元损伤 保护作用 人脑源性神经营养因子 基因治疗 

分 类 号：R741[医药卫生—神经病学与精神病学] R394[医药卫生—临床医学]