HIF-1参与K_(ATP)通道对神经元缺氧损伤保护作用  

Protective effect of HIF-1 mediates ATP-sensitive K+ channel on hippocampal neurons with chronic hypoxia

作　　者：符丰华[1] 沈阿丹[2] 黄小舟[3] 李勃兴[4] 黄潋滟[4] 

机构地区：[1]广州军区机关门诊部保健科,广东510515 [2]广州军区广州总医院 [3]中山大学第三附属医院 [4]南方医科大学公共卫生与热带医学学院

出　　处：《中国公共卫生》2010年第8期989-990,共2页Chinese Journal of Public Health

基　　金：国家自然科学基金(30900581)

摘　　要：目的探讨三磷酸腺苷(ATP)敏感性钾通道(KATP通道)在缺氧中对海马神经元的保护作用机制。方法比较对照组、单纯缺氧组、KATP通道激动剂+缺氧组、KATP通道阻断剂+缺氧组中神经元缺氧诱导因子1α亚基(HIF-1α)的蛋白表达、DNA断裂、以及神经元存活情况。结果试验持续8,12,24 h后,正常氧分压组细胞存活率为(100±0.98)%,缺氧8,12,24 h后,细胞的存活率分别降至(85.76±3.31)%,(80.13±1.76)%,(72.24±3.87)%,差异均有统计学意义(P<0.05);缺氧12,24 h后,缺氧+二氮嗪组细胞凋亡率分别为(8.1±3.1)%,(18.4±2.3)%,缺氧+甲糖宁组分别为(32.5±1.6)%,(45.7±3.4)%,与单纯缺氧组的(20.3±2.2)%,(31.6±1.7)%比较,差异均有统计学意义(P<0.05)。结论 KATP通道可以通过上调HIF-1α的蛋白表达水平,对缺氧中的海马神经元起到保护作用。Objective To study the mechanisms of KATP channels protection on hippocampal neurons against apoptosis induced by chronic severe hypoxia.Methods The hypoxia-inducible factor 1α（HIF-1α） expression,DNA fraction,and cell apoptosis in control group,hypoxia group,hypoxia group treated with KATP channels antagonist and hypoxia group treated with KATP channels agonist were examined.Results After a 12-hour＇s exposure to oxygen concentration of 0%,diazoxide（100 μM）,and KATP channels agonist,HIF-1α expression was increased and the hypoxic induced apoptosis was reduced.In contrast,tolbutamide（100 μM）,the KATP channels antagonist blocking the cellular sulphonylureas receptor,significantly rose the hypoxic-induced apoptosis but down-regulated HIF-1α expression.Conclusion KATP channels protect hippocampal neurons against chronic severe hypoxia via down-regulation of HIF-1α.

关 键 词：ATP敏感性钾通道 重度缺氧 海马神经元 缺氧诱导因子 

分 类 号：Q42[生物学—神经生物学]