抗精神病药奎硫平对大鼠海马神经元死亡和细胞周期的影响

目的：探讨抗精神病药奎硫平对谷氨酸损伤的海马神经元凋亡、坏死及细胞周期的影响，阐明其对神经系统的作用机制。方法：采用体外原代培养的大鼠海马神经元，复制谷氨酸损伤模型，实验分为正常对照组、谷氨酸损伤组和奎硫平（0.1、1.0、10.0、50.0、100.0、200.0和500.0 μmol?L^-1）组，在体外通过流式细胞术（FCM）测定奎硫平应用前后神经元凋亡、坏死和细胞周期的改变。结果：谷氨酸损伤组较正常对照组细胞凋亡率增加 (P<0.01 )；与谷氨酸损伤组比较，50.0~ 200.0 μmol?L^-1奎硫平组细胞凋亡率降低（P<0.05，P<0.01）。谷氨酸损伤组坏死细胞较正常对照组升高2.9倍 (P<0.05 )；与谷氨酸损伤组比较，0.1 μmol?L^-1奎硫平组坏死细胞比例降低 (P<0.05 )，为谷氨酸损伤组的52.0%。与正常对照组比较，谷氨酸损伤组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期细胞百分数变化不明显。与谷氨酸损伤组比较，200.0 μmol?L-1奎硫平组G0/G1期细胞百分数降低 (P<0.05 )，为谷氨酸损伤组的68.9%；S期细胞百分数升高 (P<0.05 )，为谷氨酸损伤组的3.4倍。结论：奎硫平能够抵抗谷氨酸诱导的神经元损伤，减少细胞凋亡和坏死，改变细胞周期进程。

Effect of quetiapine on death and cell cycle of rat hippocampus neurons

Objective To investigate the effects of antidepressant quetiapine on the apoptosis,necrosis and cell cycle of the hippocampus neurons injured by glutamate(Glu),and to demonstrate the mechanism of quetiapine on nervous system.Methods Primary cultured hippocampal neurons were injured with Glu.Normal control group, Glu injury group and quetiapine(0.1,1.0,10.0,50.0,100.0,200.0,and 500.0μmol·L-1)group were set up.The changes in apoptosis,necrosis and cell cycle of neurons were detected by FCM before and after administration with quetiapine.Results Compared with normal control group,the percentage of apoptotic neurons in Glu injury group was increasd(P<0.01);compared with Glu injury group,the apoptotic rates in 50.0-200.0μmol·L-1 quetiapine groups were decreased(P<0.05,P<0.01).The necrotic rate in Glu injury group was increased to 2.9times compared with normal control group(P<0.05);compared with Glu injury group,the necrotic rate of neurons in 0.1μmol·L-1 quetiapine group was decreased(P<0.05).Compored with normal control group,the percentage of neurons in G0 /G1 phase in Glu injury group was increased(P<0.001),the percentage of of neurons in S phase was decreased(P<0.01),and the percentage of neurons in G2 +M phase didn' t change significantly.Compared with Glu injury group,the percentage of neurons in G0 /G1 phase in 200.0μmol·L-1 quetiapine group was decresed,which was decreased to 68.9% of that in Glu injury group,and the percentage of neurons in S phase was increased to 3.4times of that in Glu injury group(P <0.05). Conclusion Quetiapine can prevent the hippocampal neurons from the damage induced with Glu,decrease the apoptosis and necrosis,and change the cell cycle.