抗抑郁药万拉法新和氟西汀对大鼠神经的保护作用

Neuroprotection of venlafaxine and fluoxetine

目的:探讨抗抑郁药万拉法新和氟西汀对谷氨酸损伤的海马神经元的神经保护作用。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以模拟抑郁症时的病理改变;实验分为正常对照组、谷氨酸损伤组、谷氨酸损伤+万拉法新及+氟西汀各给药组(50、100、200及500μmol.L-1或10、100及500μmol.L-1);应用MTT法分别检测万拉法新和氟西汀对谷氨酸损伤大鼠海马神经元存活率的影响,并用分光光度法测定乳酸脱氢酶(LDH)的释放情况以及SOD活性的改变。结果:谷氨酸使大鼠海马神经元存活率降至正常的50%(P<0.05);谷氨酸损伤+万拉法新组(100和200μmol.L-1)神经元存活率均高于谷氨酸损伤组(P<0.05或P<0.01),而谷氨酸损伤+氟西汀各组神经元存活率无升高。谷氨酸损伤组LDH的释放急剧升高,约是正常对照组的7.4倍;两药物均能不同程度地减少LDH的释放。谷氨酸损伤组与正常对照组比较,SOD活性明显下降(P<0.01);与谷氨酸损伤组比较,万拉法新组(10和100μmol.L-1)SOD活性均明显升高(P<0.001),谷氨酸损伤+氟西汀组(100和500μmol.L-1)SOD活性均降低(P<0.05)。结论:抗抑郁药万拉法新和氟西汀都具有一定的神经保护作用,且万拉法新神经保护作用强于氟西汀。

Objective To investigate the neuroprotection of antidepressants venlafaxine and fluoxetine on the hippocampus neurons injured by glutamate. Methods Primary cultured hippocampus neurons were injured with glutamate to mimic the pathological changes in depression. Four groups were divided as control, glutamate, venlafaxine and fluoxetine administration group. The survival rate of neurons was detected with MTT method. LDH release and SOD activity were detected by spectrophometry. 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 venlafaxine as compared with those in glutamate group （P〈0.05 or P〈0.01）. However, the survival rates of neurons were not increased after administration with fluoxetine. The LDH release of neurons injured with glutamate increased significantly, which was 7. 4-fold of control group. However, after administration with two kinds of antidepressants LDH release from neurons injured with glutamate decreased in varying degrees as compared with that in glutamate group. The SOD activity of neurons in hippocampus injured with glutamate decreased significantly （P〈0.01）, nevertheless, the administration of venlafaxine can reverse the parameter （P〈0. 001）, but the activities of SOD in fluoxetine groups （100 and 500 μmol·L^-l） decreased significantly （P〈0. 05） Conclusion Antidepressant venlafaxine and fluoxetine both have certain neuroproteetion, however, venlafaxine has greater neuroprotection compared with fluoxetine.