抗抑郁药奥氮平对大鼠海马神经细胞凋亡和细胞周期的影响

Effects of olanzapine on apoptosis and cell cycle of hippocampus neurons in rats

目的:探讨抗抑郁药物奥氮平对谷氨酸(Glu)损伤的大鼠海马神经元凋亡、坏死和细胞周期的影响,阐明奥氮平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,细胞分为正常对照组、Glu损伤组和奥氮平+Glu损伤组,在体外通过流式细胞术测定各组神经元细胞凋亡率、坏死率和细胞周期的改变。结果:与正常对照组比较,其他组细胞凋亡率增加(P<0.01);与Glu损伤组比较,10.0μmol·L-1奥氮平+Glu损伤组细胞凋亡率降低(P<0.01)。与正常对照组比较,Glu损伤组神经元坏死率升高2.9倍(P<0.05);与Glu损伤组比较,100.0和200.0μmol·L-1奥氮平+Glu损伤组神经元坏死率降低(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<0.01),S期细胞百分数下降(P<0.01),G2+M期变化不明显;而与Glu损伤组比较,50.0和100.0μmol·L-1奥氮平+Glu损伤组G0/G1期细胞比例下降为Glu损伤组的79.9%和62.6%(P<0.05或P<0.01);S期细胞比例上升为Glu损伤组的2.5和3.8倍(P<0.05或P<0.01)。结论:奥氮平能够抵抗Glu诱导的神经元凋亡和坏死,改变细胞周期进程。

Objective To investigate the effects of antidepressant olanzapine on the apoptosis, death and cell cycle of hippocampus neurons of the rats injured by glutamate （Glu）, and to illuminate the mechanism of neuroprotive effect of olanzapine. Methods The primary cultured hippocampal neurons were injured with Glu to set up Gluinjured models. The neurons were divided into normal control group, Glu injury group and olanzapine＋Glu injury group. The changes of apoptotic rate, death rate and cell cycle of neurons were detected by FCM, respectively. Results Compared with normal control group, the apoptotic rate of neurons in the other groups were increased （P〈0.01） ; compared with Glu injury group, the apoptotic rate of cells in 10.0μmol·L^-1 olanzapine＋Glu injury group was decreased （P%0.01）. Compared with normal control group, the death rate of neurons was up to 2.9 times of that in Glu injury group （P〈0.05） ; compared with Glu injury group, the death rates of neurons in 100. 0 and 200. 0 μmol·L^-1 olanzapineq-Glu groups were decreased （P〈0.05 or P〈0. 01）. Compored with normal control group, the percentage of neurons in G0/G1 phase in Glu injury group was increased （P〈0.01）, and the percentage of neurons in S phase was decreased （P〈0.01）, but the percentage of neurons in G2 ＋M phase didn＇t change significantly; compared with Glu injury group, the percentages of G0/G1 phase in 50.0 and 100. 0μmol·L^-1 olanzapineq-Glu injury groups were decreased to 79.9% and 62. 6% of that in Glu injury group （P〈0.05 or P〈0.01）. and the percentage of neurons in S phase were up to 2.5 and 3.8 times of that in Glu injury group （P〈0.05 or P〈0.01）. Conclusion Olanzapine can prevent the apoptosis and death of hippocampal neurons induced by Glu, and change the cell cycle.