摘要
目的研究KATP通道开放剂埃他卡林(iptakalim,Ipt)对心肌细胞氧化应激损伤的保护作用,并探究其作用机制。方法采用200μmol.L-1的过氧化氢(H2O2)损伤体外培养的乳鼠心肌细胞2 h,建立氧化应激心肌细胞损伤模型;以二氮嗪(diazoxide,Dia)作为阳性对照药物,采用生物化学法检测各处理组细胞培养液中乳酸脱氢酶(lactate dehydrogen-ase,LDH)活性、超氧化物歧化酶(superoxide dismutase,SOD)活性及MTT法检测心肌细胞损伤程度,反映埃他卡林对该模型的影响。结果过氧化氢损伤后,细胞存活率降低,LDH释放量明显升高,SOD活力下降;埃他卡林预处理后,细胞培养液中LDH活性较过氧化氢处理组降低(P<0.05),SOD活性升高(P<0.05),细胞存活率浓度依赖性升高(P<0.01)。该保护作用可被线粒体KATP通道阻断剂5-羟基癸酸酯(5-HD)拮抗,也可被KATP通道阻断剂格列本脲(glibenclamide,Gli)阻断。结论埃他卡林对H2O2造成氧化应激损伤的心肌细胞具有明显的保护作用,其保护作用与线粒体膜和细胞膜的KATP通道激活有关。
Aim To investigate the protective effects of iptakalim,a new ATP-sensitive potassium channel opener,on cardiomyocytes injury induced by oxidative stress and the mechanism of iptakalim.Methods The model of injured cardiomyocytes induced by oxidative stress was established via culture with hydrogen peroxide at the concentration of 200 μmol·L-1 for 2 hours.Diazoxide group was treated with diazoxide at the concentration of 100 μmol·L-1 and iptakalim group was treated with iptakalim at the concentration of 0.01~100 μmol·L-1 before cardiomyocytes injury was induced by hydrogen peroxide.We measured the activity of lactate dehydrogenase（LDH）,superoxide dismutase（SOD） in cardiomyocytes′ culture solution and used a method of MTT to detect the injury of cardiomyocytes.Results Compared with control group,in model group viability of cardiomyocytes was significantly decreased,the level of LDH in culture solution was significantly increased and the activity of SOD was significantly decreased.Pretreatment with iptakalim could cause a concentration-dependent increase of cell viability（P0.01）,decrease the LDH release（P0.05） and increase the SOD activity（P0.05）.5-HD and glibenclamide could reverse the effect of iptakalim.Conclusion Iptakalim has significant protective effects on the cardiomyocytes injury induced by hydrogen dioxide.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2011年第4期497-500,共4页
Chinese Pharmacological Bulletin
基金
国家重大新药创制科技重大专项(No2008ZX09101-006
2009ZX09301-002)
