齐拉西酮对脂多糖损伤的海马神经元活性及磷酸化细胞外信号调节激酶1／2和B细胞淋巴瘤因子2表达的影响  

Effects of ziprasidone on the cell viability and the expression of phosphorylated extracellular signal- regulated MAP kinases 1/2 and B cell lymphoma/lewkmia-2 in lipopolysaccharides injured hippocampal-derived neurons

作　　者：乔昱婷[1] 彭正午[1] 薛芬[1] 潘永珍[1] 陈云春[1] 谭庆荣[1] 

机构地区：[1]第四军医大学附属西京医院心身科,西安710032

出　　处：《中华精神科杂志》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）

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.

关 键 词：海马 神经元 细胞外信号调节MAP激酶类 淋巴瘤 B细胞 脂多糖类 齐拉西酮 

分 类 号：R749.3[医药卫生—神经病学与精神病学]