Janin Y, Qian Y Z, Hoag J B, Elliott G T, Kukreja R C
Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
J Cardiovasc Pharmacol. 1998 Sep;32(3):337-42. doi: 10.1097/00005344-199809000-00001.
We sought to determine the role of opening of adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP) channel) in monophosphoryl lipid A (MLA)-induced myocardial protection after ischemia/reperfusion (I/R) in rabbit. We used 5-hydroxydecanoate (5-HD), an ischemia-selective inhibitor of K(ATP) channel, to block MLA-stimulated cardiac protection. Four groups of rabbits were studied: group I, MLA-vehicle; group II, MLA; group III, MLA + 5-HD; and group IV, 5-HD only. MLA (35 microg/kg, i.v.) or vehicle were given 24 h before I/R. 5-HD (5 mg/kg) was given 15 min before ischemia. All rabbits underwent 30-min coronary occlusion, followed by 3-h reperfusion. Area at risk was delineated by injection of Evan's blue, and infarct size was determined by tetrazolium staining. Pretreatment with MLA reduced infarct size (percentage of area at risk) from 40+/-8.6% to 15.1+/-1.5%. The infarct size increased to 51.9+/-5.8% with 5-HD in MLA-treated rabbits. 5-HD did not alter infarct size significantly when given in vehicle-treated control rabbits. These data suggest that MLA exerts its protective effect through activation of K(ATP) channel.
我们试图确定三磷酸腺苷（ATP）敏感性钾通道（K(ATP)通道）开放在兔缺血/再灌注（I/R）后单磷酰脂质A（MLA）诱导的心肌保护中的作用。我们使用5-羟基癸酸（5-HD），一种K(ATP)通道的缺血选择性抑制剂，来阻断MLA刺激的心脏保护作用。研究了四组兔子：第一组，MLA-溶剂对照组；第二组，MLA组；第三组，MLA + 5-HD组；第四组，仅5-HD组。在I/R前24小时给予MLA（35微克/千克，静脉注射）或溶剂。在缺血前15分钟给予5-HD（5毫克/千克）。所有兔子均经历30分钟的冠状动脉闭塞，随后进行3小时的再灌注。通过注射伊文思蓝勾勒出危险区域，并用四氮唑染色确定梗死面积。MLA预处理使梗死面积（危险区域的百分比）从40±8.6%降至15.1±1.5%。在接受MLA治疗的兔子中，5-HD使梗死面积增加至51.9±5.8%。在接受溶剂治疗的对照兔子中给予5-HD时，梗死面积没有显著改变。这些数据表明，MLA通过激活K(ATP)通道发挥其保护作用。
