喹硫平对小鼠脑缺血致神经元损伤及其机制的实验研究

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.

Abstract：

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 rain.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 isehemia 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.

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

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 rain.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 isehemia 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.