抗精神病药奎硫平的神经保护作用

Neuroprotective effect of antipsychotic drug quetiapine

目的:探讨抗精神病药奎硫平的神经保护作用,阐明其神经保护作用的机制。方法:采用体外原代培养的大鼠海马神经元,复制谷氨酸(Glu)损伤模型以模拟抑郁症时的病理改变。实验分为正常对照组、Glu损伤组和奎硫平给药组。体外MTT法检测各组神经元存活率,酶学检测试剂盒测定不同浓度(50、100、200和500μmol.L-1)奎硫平应用前后乳酸脱氢酶(LDH)的释放水平、谷胱甘肽(GSH)水平、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:与正常组比较,Glu损伤组神经元存活率降低,约为正常的50%(P<0.05);与Glu损伤组比较,奎硫平在200μmol.L-1时神经元存活率升高(P<0.05)。Glu损伤组LDH的释放急剧升高,是正常组的7.4倍(P<0.001);与Glu损伤组比较,奎硫平组LDH的释放减少(P<0.01)。Glu损伤组的GSH的量下降,为对照组的9.2%(P<0.05),与Glu损伤组比较,奎硫平给药组GSH水平升高(P<0.05)。与正常组比较,Glu损伤组SOD活性明显下降(P<0.01);与Glu损伤组比较,奎硫平给药组SOD活性均升高(P<0.001)。Glu损伤组MDA水平升高,奎硫平给药组MDA水平较Glu损伤组明显下降(P<0.01)。结论:奎硫平具有神经保护作用,其机制可能与其升高GSH水平和SOD活性,降低MDA的含量有关。

Objective To investigate the neuroprotective effect of antipsychotic drug quetiapine and to demonstrate the mechanism of neuprotective effect.Methods Primary cultured hippocampal neurons were injured with glutamate（Glu） to set up Glu-injured model and to simulate the pathological changes in depression.Three groups were included in the experiment：control group,Glu model group and quetiapine administration group.The survival rates in various groups were detected by MTT method;the release level of LDH,the activity of GSH,the activity of SOD,and the level of MDA were detected before and after treated with different doses of quetiapine（50,100,200 and 500 μmol·L-1） by enzyme detection kits.Results The survival rate of neuron in Glu model group was decreased compared with control group,almost 50% of normal data（P0.05）;but compared with Glu group,the rate was increased when the concentration of quetiapine was 200 μmol·L-1（P0.05）.The LDH release level in Glu model group was increased dramatically compared with control group,up to 7.4 times of control group（P0.001）;compared with Glu group,the LDH release level was decreased in quetiapine group（P0.01）.The GSH activity in Glu model group was decreased to 9.2 % of control group（P0.05）,which was increased in quetiapine group compared with Glu model group（P0.05）.The SOD activity in Glu model group was decresded significantly compared with control group（P0.01）,which was 3.8 times of that in Glu model group when the concentration of quetiapine was 10 μmol·L-1（P0.001）.The MDA level in Glu model group was increased,nevertheless,which was reduced in quetiapine administration group compared with Glu model group（P0.01）.Conclusion Quetiapine possesses the neuroprotection and the mechanism may involve that it can elevate the GSH activity and SOD activity as well as decrease the level of MDA.