线粒体膜钾通道阻断剂在硫化氢对大鼠心功能调节的意义  

Hydrogen sulfide induce negative inotropic effect in isolated hearts via KATP channel and mitochondria membrane KATp channel

作　　者：孙燕[1] 张素清[1] 金红芳[1] 唐朝枢[2] 杜军保[1] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学教育部分子心血管学重点实验室

出　　处：《中华心血管病杂志》2009年第2期161-164,共4页Chinese Journal of Cardiology

基　　金：国家长江学者奖励计划;国家杰出青年科学基金项目资助（30425010）;国家自然科学基金项目资助（30571971）;国家自然科学基金重点项目资助（30630031）;国家重点基础研究发展规划项目资助（2006CB503807）

摘　　要：目的观察线粒体膜K。通道特异性阻断剂5-羟基葵酸盐（5-hydroxydecanoate，5-HD）对硫化氢（H2s）灌流的大鼠离体心脏心功能的影响，以探讨线粒体膜K。通道阻断剂在H2S调节心功能过程中的意义。方法应用Langendorff灌流大鼠离体心脏，用生理浓度NaHS（100μmol／L）持续灌流20min，测量心率、左室内压差（ALVP=左室收缩压-左室舒张压）、左室内压变化速率（±dp／dtmax）、冠状动脉流量等指标，分别应用非特异性KATP通道阻断剂格列苯脲、线粒体膜K。TP通道阻断剂5-HD预灌流，后给予生理剂量NaHS灌流，观察其是否可以阻断H2S的心功能效应。结果生理剂量NariS持续灌流20min内，可以显著抑制±dp／dtmax及ALVP（P〈0.05），而对心率、冠状动脉流量几乎没有影响。非特异性K。开通道阻断剂格列苯脲及线粒体膜K。通道阻断剂5-HD均可以大部分阻断生理剂量NariS对心功能的抑制效应。结论内源性H2S可以通过开放线粒体膜KATp通道，产生对心肌的负性肌力调节作用。Objective Hydrogen sulfide （H2S） dilates blood vessels in vivo and in vitro probably by opening vascular smooth muscle K^＋ -ATP channels. The study was designed to observe the role of mitoehondria membrane KATP channel blocker（5-HD） in the regulation of cardiac function isolated perfused heart of rat with H2S. Methods The isolated rat heart was perfused in a Langendorff apparatus. After 20 minutes of stabilization, physiological concentration of Naris （ H2S donor, 100μmol/L） was continuously peffused for 20 rain in group A （ n = 6）, isolated hearts in group B （ n = 6） and C （ n = 7） were pretreated with nonspecifie KATP channel blocker glibenclamide （ 100μmol/L） or 5-HD （ 100μmol/L） for 5 minutes then perfused with Naris （100μmoL/L） for 10 minutes. Heart rate （HR）, left ventricular developed pressure （ALVP）, dp/dtmax and dp/dtmin and coronary perfusion flow （CPF） were measured. Results Post continuous perfusion of Naris at physiological concentration for 20 minutes, ALVP, dp/dtmax and dp/dtmin all significantly decreased while HR and CPF remained unchanged compared to baseline levels （all P 〈0.05）. The negative inotropie effect of H2S could partly be blocked by nonspecific KATv channel blocker glibenclamide and mitochondria membrane KATp channel blocker 5-HD. Condusion Present findings suggested that H2S at physiological concentration could produce negative inotropic effect in isolated hearts and this effect was mediated by KATp channel and mitochondria membrane KATP channel.

关 键 词：硫化氢 钾通道 心室功能 左 

分 类 号：R686[医药卫生—骨科学]