组胺对β淀粉样蛋白诱导PC12细胞阿尔茨海默病体外模型的保护作用  

Reversing effect of histamine on neurotoxicity induced by β-amyloid_(1-42)

作　　者：傅秋黎[1] 戴海斌[1] 沈耀[1] 陈忠[1] 

机构地区：[1]浙江大学医学院药理学教研室,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2007年第2期146-149,共4页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(30572176;30600757)资助项目

摘　　要：目的:观察组胺对β淀粉样蛋白1-42(Aβ42)诱导大鼠肾上腺嗜铬瘤(PC12)细胞损伤的改善作用及其相关的受体亚型。方法:运用PC12细胞,采用Aβ42构建阿尔茨海默病体外模型,以形态学和四甲基偶氮唑盐比色法为指标,观察细胞损伤和药物的改善作用。结果:Aβ42浓度依赖性诱导细胞损伤。组胺在10-7、10-6mol/L浓度时能显著改善Aβ42(5μmol/L)作用24h引起的细胞损伤,10-6mol/L保护作用最大。组胺10-6mol/L的保护作用能被组胺H2受体拮抗剂zolantidine,H3受体拮抗剂clobenpropit所逆转,但不能被H1受体拮抗剂苯海拉明所拮抗。结论:组胺能减弱Aβ42诱发的细胞损伤,可能与组胺H2,H3受体有关。Objective： To investigate the effects of histamine on the neurotoxicity induced by β-amyloid1-42 （Aβ42）in rat phaeochromocytoma （PC12） cells. Methods： The in vitro model of Alzheimer＇s disease was constructed with Aβ42-treated PC12 cells. Cell morphology and MTT assay were used to evaluate the cell toxicity and histamine effects. The different histamine antagonists were applied to investigate the involvement of receptor subtypes. Results： The neurotoxicity was induced by Aβ42 in a concentration-dependent manner,which was reversed by histamine at concentration of 10^-7, 10^-6 mol/L. The effect was reversed by H2 antagonist zolantidine and H3 antagonist clobenpropit, but not by H1 antagonist diphenhydramine. Conclusion. Histamine reduces neurotoxicity induced by β-amyloid1-42,which may be mediated by H2 and H3 receptors.

关 键 词：组氨/药理学 阿尔茨海默病/药物疗法 Β淀粉样蛋白 β淀粉样蛋白1-42 大鼠肾上腺嗜铬细胞瘤细胞 

分 类 号：R749.1[医药卫生—神经病学与精神病学]