HIF-1参与KATP通道对神经元缺氧损伤保护作用

目的 探讨三磷酸腺苷(ATP)敏感性钾通道(K_ATP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、K_ATP通道激动剂+缺氧组、K_ATP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 K_ATP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。

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

Objective To study the mechan ism s o f K_ATP channels protection on hippo campal neurons aga instapoptosis induced by chronic severe hypoxia.Methods The hypoxia inducible factor-1α(HIF-1α)expre ssion,DNA fraction,and cell apoptosis in control group,hypoxia group,hypoxia group treated with K_ATP channels antagonist and hypoxia group treated with K_ATP channels agonist were examined.Results After a 12 hours exposure to oxygen concentration of 0%,diazoxide (100 M),and K_ATP channels agonist,HIF-1α expression was increased and the hypoxic induced apoptosis was reduced.In contrast,to lbutamide(100 M),the K_ATP channels antagon istblocking the cellular sulphony lureas receptor,significantly rose the hypoxic induced apoptosis but down regulated HIF-1α expression.Conclusion K_ATP channels protect hippo campal neurons against chronic severe hypoxiavia down regulation of HIF-1α.