J4

• 基础医学 • 上一篇    下一篇

抗精神病药奥氮平的神经保护作用

王珍琦,张 萱,李鹏武,刘 扬,贾晓晶,龚守良   

  1. (吉林大学公共卫生学院 卫生部放射生物学重点实验室,吉林 长春 130021)
  • 收稿日期:2008-01-11 修回日期:1900-01-01 出版日期:2008-07-28 发布日期:2008-07-28
  • 通讯作者: 龚守良

Neuroprotection of antipsychotic olanzapine

WANG Zhen-qi,ZHANG Xuan,LI Peng-wu,LIU Yang,JIA Xiao-jing,GONG Shou-liang   

  1. Key Laboratory of Radiobiology,Ministry of Health,School of Public Health,Jilin University,Changchun 130021,China
  • Received:2008-01-11 Revised:1900-01-01 Online:2008-07-28 Published:2008-07-28
  • Contact: GONG Shou-liang

摘要: 目的:探讨抗精神病药物奥氮平对谷氨酸损伤的海马神经元存活率、乳酸脱氢酶(LDH)的释放及凋亡和坏死的影响。方法:采用体外原代培养的大鼠海马神经元,复制谷氨酸损伤模型,实验分为正常对照、谷氨酸损伤和奥氮平给药组,在体外通过MTT法检测奥氮平对神经元存活率的影响,分光光度法测定LDH的释放情况,流式细胞术(FCM)测定奥氮平应用前后神经元凋亡和坏死的改变情况。结果:谷氨酸的兴奋性神经毒性使神经元存活率降低,约为正常的50% (P<0.05);与谷氨酸损伤组比较,奥氮平浓度为200和500 μmol•L-1时其存活率升高 (P<0.05),100 μmol•L-1时明显升高 (P<0.01)。谷氨酸损伤组LDH的释放急剧升高,是正常组的7.4倍;奥氮平组与谷氨酸损伤组比较,LDH释放减少(P<0.05或P<0.01)。谷氨酸损伤组与正常对照组比较,细胞凋亡率增加 ( P<0.01 );而奥氮平作用后凋亡细胞百分数显著低于谷氨酸损伤组。谷氨酸的神经毒性使体外培养的神经元坏死细胞比例升高 ( P<0.05 );而奥氮平组与谷氨酸损伤组比较,坏死细胞比例降低(P<0.05或P<0.01)。 结论:奥氮平能够抵抗谷氨酸诱导的神经元损伤,提高神经元存活 率,减少LDH的释放,维持细胞膜的完整性,减少神经元的凋亡和坏死,具有神经保护作用 。

关键词: 神经保护作用, 谷氨酸, 神经元

Abstract: To investigate the effects of antipsychotic olanzapine on the survival rate of neurons,LDH release,percentage of apoptotic cells and death rate of the hippocampus neurons injured by glutamate. Methods Primary  cultured hippocampal neurons were injured with glutamate. Three groups were divided as control,glutamate insult and olanzapine administration groups. The survival rate of neurons was detected with MTT method and LDH release was detected by spectrophometry. The changes in percentage of apoptotic cells and death rate of neurons were detected respectively by FCM before and after administration with olanzapine. Results The  survival rate of neurons injured with the excitatory neurotoxicity of glutamate decreased to 50% of control (P<0.05). The survival rates of neurons injured with glutamate increased dramatically after administration with olanzapine as compared with those in glutamate group (P<0.05 or P<0.01). The LDH release of neurons injured with glutamate increased significantly,which was 7.4-fold of control group,however,LDH release from neurons injured with glutamate decreased after administration with olanzapine as compared with that in glutamate group. The percentages of apoptotic cells of neurons injured with glutamate increased (P<0.01 ),but oalnzapine can reverse it. The death rates of neurons injured with glutamate increased compared with control (P<0.05 ),nevertheless,the administration of olanzapine reduced the death rates of neurons injured with glutamate as compared with that in glutamate group (P<0.05,P<0.01). Conclusion Olanzapine can prevent the hippocampal neurons from the damage induced with glutamate,elevate the neuron survival rate,reduce the LDH release,keep the cell membrane intact,and decrease the percentage of apoptotic cells and death rate of neurons,which has the neuroprotection.

Key words: neuroprotection, glutamic acid, neurons

中图分类号: 

  • R971.4