β_2肾上腺素受体对Aβ_(1-40)诱导阿尔茨海默病大鼠脑内胆碱能水平的影响  

Effects of β_2-adrenergic receptor on cholinergic system in Alzheimer ’s disease rats induced by Aβ_(1-40)

作　　者：葛培兵[1] 丁高中[1] 戚晓红[2] 袁艺标[1] 周红[1] 

机构地区：[1]南京医科大学基础医学实验教学示范中心,江苏南京210029 [2]南京医科大学病理生理学系,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2012年第6期754-757,共4页Journal of Nanjing Medical University(Natural Sciences)

基　　金：南京医科大学科技发展基金(08NMUM006);南京医科大学"十二五"教育研究课题(NY222011030)

摘　　要：目的:研究β2肾上腺素受体激动剂和抑制剂对阿尔茨海默病(AD)大鼠学习记忆能力和脑内乙酰胆碱含量的影响。方法:40只健康雄性SD大鼠随机平均分为4组:对照组、AD组、克伦特罗组和ICI118,551组。AD组给予海马内注射Aβ1-401μl(10μg),克伦特罗组和ICI118,551组同样注射Aβ1-40后分别腹腔注射克伦特罗0.5 mg/kg和ICI118,551 1 mg/kg。对照组注射生理盐水。Y迷宫检测各组大鼠的学习记忆能力后检测海马内胆碱酯酶(AChE)和乙酰转移酶(ChAT)的含量,Nissle染色观察海马CA1区神经元的形态学改变。结果:与AD组相比,克伦特罗组的学习记忆能力明显下降(P<0.01),海马ChAT、AChE活力下降,CA1区神经元凋亡明显(P<0.01);而ICI118,551组学习记忆能力、海马ChAT、AChE活力均较AD组提高,海马神经元的损伤情况较AD组有所改善(P<0.05)。结论:β2肾上腺素受体激动剂、抑制剂分别能加重和减轻AD病变,其机制可能与改变脑内胆碱能水平有关。Objective：To investigate the agonist and inhibitor effects of β2-adrenergic receptor （β2-AR） on learning and memory capacities and the level of acetylcholine in hippocampus of Alzheimer＇s disease（AD）rats. Methods：Forty healthy male Sprague Dawley rats were randomly and equally divided into 4 groups,ie,saline-injected group,AD group,clenbuterol group and ICIl18,551 group. The AD rat model was established by amyloid-β1-40 （Aβ1-40） injection into hippocampus. Then the clenbuterol group and I- CI118,551 group were peritoneal injected by clenbuterol of 0.5 mg/kg and ICI118,551 of 1 mg/kg respectively for 20 days after they were injected Aβ1-40 injection. The learning and memory ability were determined by Y-maze,and the activity of AChE and ChAT in hippocampus was tested by chemistry method. Nissle staining was used to verify neuron apoptosis. Results：Compared with the AD rats,the learning and memory ability of rats injected with clenbuterol were significantly decreased（P 〈 0.01 ）,correspondingly,the activity of AChE and ChAT decreased. While in the rats of the ICI118,551 group, both their learning and memory ability and the activity of AChE and ChAT were increased compared with those in the AD rats （P 〈 0.05）. Conclusion：The β2-AR agonist clenbuterol might aggravate the injury induced by Aβ1-40,while the I32-AR selective antagonist ICI 118,551 can improve AD pathological process. These results suggested that the level of acetylcholine in brain tissue may be involved in the possible mechanisms of AD.

关 键 词：阿尔茨海默病 Β2肾上腺素受体 乙酰胆碱 学习记忆 β样淀粉样蛋白 

分 类 号：R741[医药卫生—神经病学与精神病学]