盐酸埃他卡林对H_2O_2所致PC12细胞损伤的保护  

Effects of iptakalim hydrochloride on H_2O_2 induced cytotoxicity in pheochromocytoma(PC12) cells

作　　者：柴怡[1] 丁建花[1] 李皓[1] 胡刚[1] 

机构地区：[1]南京医科大学药理学与神经生物学系

出　　处：《中国临床药理学与治疗学》2005年第4期377-381,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家创新药物基础研究重大项目 (№ 9690 10 10 1) ;国家自然科学基金资助项目 (№ 3 9970 846)

摘　　要：目的:研究KATP 通道开放剂盐酸埃他卡林(iptakalimhydrochloride ,Ipt)对H2 O2 所致PC12细胞损伤的保护作用及其作用机制。方法:采用培养的PC12细胞,MTT法测定细胞存活率,HPLC法测定细胞培养液中谷氨酸(Glu)的含量,荧光法测定胞内钙离子([Ca2 +]i)浓度。结果:Ipt可浓度依赖性的拮抗H2 O2 介导的细胞毒性,提高细胞生存率,降低胞外Glu的释放以及胞内Ca2 +浓度。该保护作用可被2 0 0 μmol·L- 15 - HD(线粒体KATP通道阻断剂)部分拮抗。结论:Ipt可拮抗H2 O2 介导的细胞损伤作用,该保护作用可能与线粒体ATP敏感性钾通道相关。AIM: To investigate the protective effects and mechanisms of iptakalim hydrochloride(Ipt)on H_2O_2 induced neurotoxity. METHODS: Neurotoxity injury was induced by H_2O_2 in PC12 cells. The cell viability was tested by MTT assay. The glutamate released from PC12 cells was measured by HPLC combined with fluorescent detector analysis. Changes in the intracellular free Ca 2+ concentration ([Ca 2+ ]_i) were determined in fluo-3 AM loaded PC12 cells. RESULTS: Ipt (1, 10 and 100 μmol·L -1 ) markedly mitigated H_2O_2-induced neurotoxity, 10 μmol·L -1 Ipt inhibited the release of glutamate and the increase of [Ca 2+ ]_i induced by H_2O_2 .The protective effects was incompletely blocked by 5-HD which is a mitochondrial K_ ATP channels antagnist. CONCLUSION: Ipt provides neuroprotective effects on H_2O_2 induced cytoxixity in cultured PC12 cells and the protective effects may be partially related with mitochondrial KATP channels.

关 键 词：盐酸埃他卡林 ATP敏感性钾通道 PC12细胞 氧化应激 谷氨酸 游离钙 

分 类 号：R971.1[医药卫生—药品]