K_(ATP)通道对缺氧海马CA1区神经元损伤保护作用的机制

PROTECTION MECHANISMS OF ATP-SENSITIVE K^+ CHANNELS ON HIPPOCAMPAL CA1 NEURONS DURING CHRONIC SEVERE HYPOXIA

目的:探讨KATP通道在缺氧中对海马CA1区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p53 mRNA的表达、DNA断裂、以及神经元存活情况。结果:将神经元暴露在氧浓度为0%的缺氧环境中12h,KATP通道的激动剂二氮嗪(diazoxide,100μmol/L)显著降低p53 mRNA的表达量及细胞的凋亡数量。KATP通道的阻断剂甲糖宁(tolbutamide,100μmol/L)使p53mR-NA表达量显著增加,细胞的凋亡数量也随之显著增加。p53的特异性阻断剂曲古抑菌素(trichostatin,TSA)可以逆转甲糖宁(tolbutamide,100μmol/L)的作用。结论:KATP通道可以通过下调p53 mRNA的表达水平,对缺氧中的海马CA1区神经元起到保护作用。

Aim：To study the protection mechanisms of KATP channels on hippocampal CA1 neurons during chronic severe hypoxia.Methods：p53 expression,DNA fraction,and cell apoptosis were examined in cultured hippocampal neurons in control group,hypoxia group,hypoxia group treated with KATP channels antagonist and hypoxia group treated with KATP channels agonist.Results：In the group of a 12 h long exposure to oxygen concentration of 0%,diazoxide（100 μmol/L）,the KATP channels agonist,reduced p53 expression and the hypoxia-induced apoptosis.In contrast,tolbutamide（100 μmol/L）,the KATP channels antagonist,significantly rose p53 expression and the hypoxia-induced apoptosis,which could be reversed by p53 inhibitor TSA.Conclusion：KATP channels protect hippocampal neurons against chronic severe hypoxia by suppressing p53 expression.