抗抑郁药万拉法新对大鼠海马神经细胞凋亡和细胞周期的影响

J4 ›› 2011, Vol. 37 ›› Issue (4): 577-581.

抗抑郁药万拉法新对大鼠海马神经细胞凋亡和细胞周期的影响

张萱^1,2, 刘纯岩³, 王英男⁴, 关松磊¹, 王珍琦¹

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；2.吉林大学第二医院科教科|吉林长春130041；3.吉林大学第二医院放射线科|吉林长春1300414.吉林农业大学农机系|吉林长春130118）〖

收稿日期:2011-04-07 出版日期:2011-07-28 发布日期:2011-07-28
通讯作者: 王珍琦 E-mail:（Tel：0431-85619443，E-mail：wangzhenqi88@yahoo.com.cn）
作者简介:张萱（1972-）,女|吉林省九台市人|教授|医学博士|主要从事抗抑郁药神经保护作用的研究。
基金资助:
国家自然科学基金资助课题（30800363）

Effect of venlafaxine on apoptosis and cell cycle of rat hippocampus neurons

ZHANG Xuan^1,2,LIU Chun-Yan³ WANG Yang-Nan⁴, GUAN Song-Lei¹, WANG Zhen-Qi¹

(1. Key Laboratory of Radiobiology,Ministry of Health,School of Public Health,Jilin University,Changchun 130021,China;2.Department of Science and Education,Second Hospital,Jilin University,Changchun 130041,China;3.Department of Radiology,Second Hospital,Jilin University,Changchun 130041,China;4. Department of Agriculture Machine,Jilin Agricultural University,Changchun 130118,China)

Received:2011-04-07 Online:2011-07-28 Published:2011-07-28

摘要/Abstract

摘要：

目的：探讨抗抑郁药物万拉法新对谷氨酸（Glu）损伤的海马神经元凋亡、坏死细胞周期的影响，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Glu损伤模型，实验分为正常对照、Glu损伤和万拉法新给药组，在体外通过FCM测定万拉法新应用前后神经元凋亡、坏死和细胞周期的改变情况。结果：与正常对照组比较，Glu损伤组凋亡细胞增加 (P<0.01)。与Glu损伤组比较，万拉法新组低浓度抑制细胞凋亡，10 μmol·L-1时凋亡细胞百分数降低(P<0.05);而较高浓度反而促进凋亡，100 μmol·L^-1时凋亡百分数明显升高(P<0.01）。Glu损伤组坏死细胞较正常对照组比例升高2.9倍 ( P<0.05 )；与Glu损伤组比较，万拉法新降低坏死细胞比例 (P<0.05或P<0.01)。与正常对照组比较，Glu损伤组G0/G1期细胞百分数增加 (P<0.001)，S期细胞百分数下降（P<0.01），G₂+M期变化不明显。与Glu损伤组比较，万拉法新组G₀/G₁期细胞百分数表现为下降的趋势，其浓度在100和200 μmol·L^-1时分别下降为Glu损伤组的64.5%和50.8% (P<0.05)，500 μmol·L^-1 时降为57.4% (P<0.01)；S期细胞百分数呈上升趋势，100、200和500 μmol·L^-1时分别为Glu损伤组的3.6、4.7和4.2倍 (P<0.01)。结论：万拉法新能够抵抗Glu诱导的神经元损伤，改变细胞周期进程，具有神经保护作用。

关键词: 万拉法新；神经保护作用；谷氨酸；神经元

Abstract:

Abstract:Objective
To investigate the effects of antidepressant venlafaxine on the apoptotic cell percentage,death rate and cell cycle of the hippocampus neurons injured by glutamate(Glu) and demonstrate the neuroprotection mechanism of venlafaxine.Methods The primary cultured hippocampal neurons were used to set up Glu injured model.Three groups were included in the experiment: control group,Glu model group and venlafaxine administration group.The changes in apoptotic cell percentage,death rate and cell cycle of neurons were detected respectively by FCM before and after administration with venlafaxine.Results The apoptotic cell percentage in Glu model group was increasd compared with control group (P<0.01),but venlafaxine could reverse it.Compared with Glu model group,in venlafaxine administration group the apoptosis was suppressed at low concentrations,the apoptotic cell percentage was decreased at 10 μmol·L^-1 venlafaxine （P<0.05),nevertheless,the apoptosis was promoted at high concentrations,the apoptotic cell percentage was increased dramatically when treated with 100 μmol·L^-1 venlafaxine (P<0.01).The death rate of neurons in Glu model group was increased compared with control group(P<0.05 ),the death rate of neurons was reduced in venlafaxine administration group compared with Glu model group (P<0.05 or P<0.01).Compared with control group,the apoptotic cell percentage of G0/G1 phase in Glu model group was increased (P<0.001),the apoptotic cell percentage of S phase was decreased (P<0.01),the cell percentages of G^₂+M phase didn’t change significantly.The apoptotic cell percentages in venlafaxine administration groups showed an decreasing trend at G₀/G₁ phase,which decresed to 64.5% and 50.8% of that in Glu model groups when treated with 100 and 200 μmol·L^-1 venlafaxine (P<0.05).The apoptotic cell percentages of S phase in venlafaxine administration groups were increased,which were 3.6,4.7 and 4.2 times of that in Glu model group when treated with 100,200 and 500 μmol·L^-1 venlafaxine respectively (P<0.01).Conclusion Venlafaxine can prevent the hippocampal neurons from the damage induced with Glu,elevate the neuron survival rate,reduce the LDH release,keep the cell membrane intact,and decrease the apoptotic cell percentage and death rate of neurons,which has the neuroprotection.

Key words: venlafaxine;neuroprotection;glutamate;neuron

中图分类号:

R-332

张萱, 刘纯岩, 王英男, 关松磊, 王珍琦. 抗抑郁药万拉法新对大鼠海马神经细胞凋亡和细胞周期的影响[J]. J4, 2011, 37(4): 577-581.

ZHANG Xuan, LIU Chun-Yan, WANG Yang-Nan, GUAN Song-Lei, WANG Zhen-Qi. Effect of venlafaxine on apoptosis and cell cycle of rat hippocampus neurons[J]. J4, 2011, 37(4): 577-581.