喹硫平对小鼠脑缺血致神经元损伤及其机制的实验研究  

Experimental research of quetiapine' s effects on neuronal injury after cerebral ischemia and its mechanism

作　　者：房绍宽[1] 吴江[1] 周春奎[1] 

机构地区：[1]吉林大学第一医院神经内科,吉林长春130021

出　　处：《中风与神经疾病杂志》2009年第6期705-708,共4页Journal of Apoplexy and Nervous Diseases

基　　金：加拿大健康研究基金资助项目(MOP79132)

摘　　要：目的研究喹硫平对小鼠脑缺血致神经元损伤的保护作用及机制。方法雄性ICR小鼠给予喹硫平10mg/kg腹腔注射14d预处理,然后闭塞双侧的颈总动脉。实验共分为4个组:假手术组、缺血组、药物对照组及药物保护组。采用Fluoro-Jade B染色观察脑缺血后海马齿状回区神经元损伤情况;采用Western blot方法检测MDA、BDNF和Bcl-xL/Bax蛋白的表达。结果缺血组与假手术组比较Fluoro-Jade B染色阳性细胞数量明显增加(P<0.01);药物保护组与缺血组比较Fluoro-Jade B染色阳性细胞数量明显减少(P<0.01)。缺血组与假手术组比较Bcl-xL/Bax比值减少(P<0.05);药物保护组与缺血组比较Bcl-xL/Bax比值增加(P<0.05)。缺血组与假手术组比较BDNF蛋白表达量减少(P<0.05);药物保护组与缺血组比较BDNF蛋白表达量增加(P<0.05)。缺血组与假手术组比较MDA蛋白表达量增加(P<0.05);药物保护组与缺血组比较MDA蛋白表达量减少(P<0.05)。结论喹硫平能够减轻小鼠脑缺血所致的神经元损伤,其机制可能与减少MDA的表达、增加Bcl-xL/Bax的比值、增加BDNF的表达有关。Objective To study the effects of quetiapine on neuronal injury after cerebral ischemia and its mechanism.Methods The mice were pre-reated with quetiapine（10mg/kg） by intraperitoneal（i.p.） injection once a day for 14 days.After that bilateral common carotid arteries were occluded for 60 min.We investigated neuronal injury in dentate gyrus of hippocampus after cerebral ischemia through Fluoro-ade B staining.We investigated MDA,BDNF and Bcl-L/Bax protein expression after cerebral ischemia through Western blot technique.Results Fluoro-Jade B staining positive cells significantly increased in ischemia group compared with sham group（P〈0.01）;Fluoro-Jade B staining positive cells significantly decreased in drug-protective group compared with ischemia group（P〈0.01）;Bcl-xL/Bax ratio decreased in ischemia group compared with sham group（P〈0.05）;and Bcl-xL/Bax ratio increased in drug-protective group compared with ischemia group（P〈0.05）.BDNF protein decreased in ischemia group compared with sham group（P〈0.05）;BDNF protein increased in drug-protective group compared with ischemia group（P〈0.05）.MDA protein increased in ischemia group compared with sham group（P〈0.05）;MDA protein decreased in drug-protective group compared with ischemia group（P〈0.05）.Conclusions Quetiapine attenuated neuronal injury after cerebral ischemia and its mechanism might be associated with decreasing MDA expression,increasing BDNF expression and increasing Bcl-xL/Bax ratio.

关 键 词：喹硫平 神经元损伤 FLUORO-JADE B 

分 类 号：R743.3[医药卫生—神经病学与精神病学]