摘要
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I／2（pERKl／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、50μmol／／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，Westernblot检测pERK1／2和Bcl-2表达水平的变化。结果齐拉西酮（5μmol／L）组处理48h的细胞活性（0．35±0．03）与LPS组（0．254-0．01）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、10μmol／L）组处理48h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、10μmol／L）组pERK1／2（1．37±0．12，1．044-0．05）和Bcl-2（0．78±0．04，0．57±0．09）的表达水平与LPS组（0．72±0．06、0．344-0．09）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（10μmol／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。
Objective To investigate the effects of ziprasidone on the cell viability and expression of the phosphorylated ERK1/2 and Bcl-2 in lipopolysaecharides （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 /xmol/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 ）. Conclnsions Tile 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.
出处
《中华精神科杂志》
CAS
CSCD
北大核心
2012年第6期359-363,共5页
Chinese Journal of Psychiatry
基金
国家自然科学基金（30870886）
