Objective To investigate the effects of ziprasidone on the cell viability and expression of the phosphorylated ERK1/2 and Bcl-2 in lipopolysaccharides (LPS) injured hippocampal-derived neurons.Methods The neurons were derived from hippocampus of newborn rats,after 5 days culturing,the cells were treated with LPS (200 μg/ml) and different concentrations of ziprasidone for 48 h.Then the cell viability,the level of LDH in the media,and the protein level of pERK1/2 and Bcl-2 were measured by the kit of WST-8,LDH and western blot,respectively.Results The cell viability in 5 μmol/L ziprasidone treated group (0.35 ± 0.03) was higher than LPS group (0.25 ± 0.01 ; P ＜ 0.01),but there were no significant differences between other ziprasidone treated groups and LPS group (P ＞ 0.05).The LDH released by neurons in 5 μmol/L[(1497.73 ± 87.55) U/L] and 10 μmol/L[(1783.16 ± 82.75) U/L]ziprasidone treated groups had significant differences compared to the LPS group [(2024.38 ± 110.54) U/L;P ＜0.01,P ＜ 0.05].However,there were no significant differences between other ziprasidone treated groups and LPS group(P ＞ 0.05).Furthermore,when detected by western blot,the expression of pERK1/2 and Bcl-2 in ziprasidone 5 μ mol/L(1.37 ± 0.12,0.78 ± 0.04) and 10 μmol/L(1.04 ± 0.05,0.57 ± 0.09)treated groups were significant higher than LPS group (0.72 ± 0.06,0.34 ± 0.09 ; P ＜ 0.01).And there were significant difference in the expression of pERK1/2 between ziprasidone 5 μmol/L and 10 μmol/L treated group (P ＜ 0.01).Conclusions The cellular damage of hippocampal-derived neurons injured by LPS could be restrained by ziprasidone,which are possibly carried out by affecting the expression of the ERK1/2 and Bcl-2,and this is one of the possible neural protective mechanism of ziprasidone.%目的 探讨齐拉西酮对脂多糖(LPS)损伤后海马神经元活性的作用及对磷酸化细胞外信号调节激酶1/2(pERK1/2)和B细胞淋巴瘤因子2(Bcl-2)表达的影响.方法 建立体外大鼠海马神经元LPS损伤细胞模型,给予不同剂量齐拉西酮(1、5、10、20、50 μmol//L)作用后,采用WST-8试剂检测细胞活性,乳酸脱氢酶(LDH)试剂盒检测LDH含量,Western blot检测pERK1/2和Bcl-2表达水平的变化.结果 齐拉西酮(5 μmol/L)组处理48 h的细胞活性(0.35 ±0.03)与LPS组(0.25±0.01)比较差异有统计学意义(P＜0.01),而其他处理组与LPS组比较差异无统计学意义(P＞0.05)；齐拉西酮(5、10 μmol/L)组处理48 h的海马神经元释放LDH[(1497.73 ±87.55)、(1783.16±82.75) U/L]与LPS组[(2024.38±110.54) U/L]比较差异有统计学意义(P＜0.01,P＜0.05),其他处理组与LPS组比较差异无统计学意义(P＞0.05)；齐拉西酮(5、10 μmol/L)组pERK1/2(1.37±0.12,1.04±0.05)和Bcl-2(0.78±0.04,0.57 ±0.09)的表达水平与LPS组(0.72 ±0.06、0.34±0.09)比较差异有统计学意义(P均＜0.01),且齐拉西酮(5μmol/L)组和齐拉西酮(10 μmol/L)组pERK1/2表达的差异有统计学意义(P＜0.05),其他处理组pERK1/2和Bcl-2的表达水平与LPS组比较差异无统计学意义(P＞0.05).结论 齐拉西酮可能通过影响pERK1/2和Bcl-2的表达来抑制LPS导致的海马神经元活性损伤,这一作用可能是齐拉西酮神经保护机制之一.
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