奥氮平对淀粉样β蛋白_(25-35)诱导的PC12细胞凋亡的保护作用

Protective effects of olanzapine against PC12 cell apoptosis induced by β-amyloid peptide 25-35

目的探讨奥氮平对淀粉样β蛋白25-35（Aβ25-35）诱导的PC12细胞凋亡的保护作用机制。方法以Aβ25-35诱导PC12细胞凋亡，采用MTT比色分析测定细胞存活率，应用Western blot检测Aβ25-35以及奥氮平对PC12细胞Bax、Caspase-3表达的影响，结果10^-14～10^-5mol／L的Aβ25-35减低PC12细胞存活率，50μmol／L及100μmol／I。奥氮平预处理24h可提高PC12细胞存活率，相同浓度Aβ25-35奥氮平预处理组与非处理组比较差异显著（P〈0．05）；0．01、2、20μmol／L Aβ25-35处理的PC12细胞Bax表达增加，50μmol／L奥氮平预处理使0．01μmol／L和20μmol／L Aβ25-35诱导的PC12细胞Bax的表达减低（P〈O．05）；2μmol／L及20μmol／L Aβ25-35处理的PC12细胞Caspase-3的表达增高，5μmol／L奥氮平预处理能抑制其表达升高，与非预处理比较差异显著（P〈O．05）。结论奥氮平可对抗Aβ25-35对PC12细胞的毒性作用，其机制可能与抑制Bax、Caspase-3的表达有关。

Objective To investigate the mechanism of the protective effects of olanzapine against apoptosis of PC12 cells induced by β- amyloid peptide 25--35 （Aβ25-35）. Methods Based on the model of apoptosis of PC12 cells induced by Aβ25-35, cell viability was determined by MTT assay. The expressions of Bax, Caspase-3 of PC12 cells induced by Aβ25-35 and olanzapine were assessed by Western blot. Results 10^-14-10^-5mol/L Aβ25-35 lowered the cell viability of PC12 cells, 50μmol/L and 100μmol/L olanzapine pretreatment enhanced the cell viability of PC12 cells, and there was significant difference compared with olanzapine non-pretreated groups （P〈0. 05）. 0. 01μmol/ L, 2μmol/L and 20μmol/L Aβ25-35 treatment up-regulated the Bax expression of PC12 cells, and 50μmol/L olanzapine pretreatment downregulated its expression, and difference was significant compared with olanzapine non-pretreated groups （P〈0. 05）. 2μmol/L and 20μmol/ L Aβ25-35 treatment up-regulated the Caspase-3 expression of PC12 cells, 50μmol/L olanzapine pretreatment down-regulated its expression, the difference was significant compared with olanzapine non-pretreated groups （P〈0. 05）. Conclusion Olanzapine can antagonize Aβ25-35 neurotoxicity to the PC12 cells. The mechanism of protection is likely related to a lowering in the Bax and Caspase-3 expression.