摘要
目的:观察ATP敏感性钾通道(KATP)开放剂二氮嗪对心肌细胞氧化应激损伤的保护作用,并探讨其作用机制。方法:采用过氧化氢(500μmol.L-1)诱导法制备大鼠培养心肌细胞氧化应激损伤模型,通过检测培养液中乳酸脱氢酶以及用流式细胞仪结合罗丹明-123和碘化丙啶双标记法检测线粒体膜电位和细胞存活状态,观察二氮嗪(100μmol.L-1)对氧化应激损伤的保护作用。结果:二氮嗪预处理后,细胞培养液中乳酸脱氢酶活性较过氧化氢处理组显著降低(P<0.01),细胞存活率升高,并可减少氧化应激造成的线粒体膜电位的丢失,其作用可被线粒体KATP通道阻断剂5-羟基癸酸酯所拮抗。结论:二氮嗪对过氧化氢造成的培养心肌细胞氧化应激损伤具有保护作用,其可能通过激活线粒体KATP通道介导。
AIM： To investigate the protective effects of Diazoxide, a selective mitOKATP opener, on the cardiac myocytes damages induced by oxidative stress and to discuss its mechanism. METHODS： Oxidative damage cell model was induced by hydrogen peroxide （H2O2 500 μmol·L^-1 ）. Lactate dehydrogenase （LDH） activities in the medium and mitoehondrial membrane potential assessed in flow eytometry by dual labelling with rhodamine- 123 （Rh-123） and propidium were measured in the diazoxide （ 100 μmol·L^-1） pretreated and un-pretreated groups. RESULTS： The level of LDH and the percentage of injured cells in H2O2 exposure group after 2 h injury were significantly higher than those in the control group （P 〈 0.01）. On the contrary, after exposure to H2O2, the Rh-123 fluorescence intensity was significantly decreased. Compared with simple injury group, pre-treatment with diazoxide （ 100 μmol·L^-1） eould obviously attenuate H2O2 induced eytotoxieity, which eould be abrogated by the mitoKATP channel blocker 5-hydroxydeeanoate （ 500 μmol·L^-1 ）. CONCLUSION： Diazoxide exerts significant protective effects against the damages induced by H2O2 in the cultured neonatal rat eardiomyoeytes, which may be mediated by activation of mitoKATP channels.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第7期806-809,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
