摘要
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.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2007年第3期257-261,共5页
Chinese Journal of Applied Physiology
基金
国家自然科学基金面上基金项目(30371575)
关键词
ATP敏感钾通道
重度缺氧
神经元
P53
ATP sensitive potassium channel
chronic severe hypoxia
neuron
p53