盐酸埃他卡林对帕金森病细胞模型谷氨酸摄取下降的影响  

Effect of Iptakalim hydrochloride on the impairment of glutamate uptake in cell models of Parkinson's disease

作　　者：杨彦玲[1] 丁建花[1] 胡刚[1] 

机构地区：[1]南京医科大学药理与神经生物学系,江苏省南京市210029

出　　处：《中国临床康复》2004年第19期3743-3745,共3页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金资助项目(39970846);国家创新药物基础研究重大项目(969010101)~~

摘　　要：目的:研究多巴胺能神经毒素对PC12细胞谷氨酸摄取的影响;探讨新型三磷酸腺苷(ATP)敏感性钾通道(ATP-sensitivepotassiumchannel,K-ATPchannel)开放剂盐酸埃他卡林(Iptakalimhydrochloride,Ipt)对神经毒素诱导的谷氨酸转运体功能下降的作用及机制。方法:放射性核素标记法测定PC12细胞L-犤3H犦-Glutamate摄取能力,MTT法测定细胞活力。结果:多巴胺能神经毒素6-羟基多巴胺(6-hydroxydopamine,6-OHDA)、N-甲基,4-苯基吡啶离子(1-methyl-4-phenyl-2,3-dihydropyridiniumion,MPP+)和鱼藤酮浓度依赖性地降低PC12细胞谷氨酸摄取:与对照组2.0±0.2相比,6-OHDA(30,50,80和100μmol/L)使摄取量降至1.6±0.1,1.0±0.3,0.8±0.1和0.5±0.1(P<0.01);MPP+(200,400,600和800μmol/L)诱导摄取量降为1.6±0.2,1.5±0.2,1.2±0.1和1.0±0.2(P<0.01);鱼藤酮(5,10,20和40nmol/L)诱发摄取量降至1.5±0.2,0.6±0.1,0.4±0.1和0.2±0.1(P<0.01)。Ipt(10μmol/L)预处理能够完全对抗6-OHDA和MPP+、部分改善鱼藤酮造成谷氨酸转运功能异常,这种保护作用可被格列苯脲(Glibenclamide,Glib)(20μmol/L)阻断。结论:谷氨酸转运体功能下降参与多巴胺能神经毒素的损伤作用;Ipt通过激活K-ATP通道促进谷氨酸摄取,对抗毒素引发的兴奋毒性。AIM:To study the effects of dopaminergic neurotoxins on PC12 glutamate transporter activity and to explore the function of ATP sensitibe potassium channel(K ATP channel) opening Iptakalim hydrochloride(Ipt) on neurotoxin induced glutamate transport dysfunction and its mechanism. METHODS:L Glutamate uptake of PC12 cells was measured by scintillation counting.The activity of PC12 cells was measured with MTT assay. RESULTS:Dopamine neurotoxin 6 hydroxydopamine(6 OHDA),1 methyl 4 phenyl 2,3 dihydropyridinium ion(MPP+) and rotenone(Rot) decreased PC12 glutamate uptake in a concentration dependent manner.Glutamate uptake activity reduced from 2.0±0.2 in control group to 1.6±0.1, 1.0±0.3,0.8±0.1,and 0.5±0.1 in 6 OHDA(30,50,80 and 100 μmol/L) treated group(P< 0.01);1.6±0.2,1.5±0.2,1.2±0.1 and 1.0±0.2 in MPP+(200,400,600 and 800 μmol/ L) treated group(P< 0.01);1.5±0.2,0.6±0.1,0.4±0.1 and 0.2±0.1 in Rot treated group(P< 0.01).Pre treatment with 10 μmol/ L Ipt significantly protected cells from glutamate uptake disorder induced by 6 OHDA,MPP+and some Rot,and this protection could be abolished by glibenclamide(Glib) (20 μmol/L). CONCLUSION:Glutamate transport dysfunction takes part in dopamine neurotoxin injury.Ipt can promote the increase of glutamate uptake, which is mediated via opening of K ATP channels,and protect cells against exitotoxicity induced by toxin.Ipt can serve as a protential therapy for Parkinson's disease and other neurodegenerative diseases.

关 键 词：盐酸埃他卡林 帕金森病 细胞模型 谷氨酸摄取下降 多巴胺能神经毒素 PC12细胞 发病机制 

分 类 号：R742.5[医药卫生—神经病学与精神病学]