Kukreja R C
Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Ann N Y Acad Sci. 1999 Jun 30;874:211-21. doi: 10.1111/j.1749-6632.1999.tb09237.x.
Heat shock (HS) and 4-monophosphoryl lipid A (MLA, a non-toxic analogue of endotoxin) protects the myocardium against ischemia-reperfusion injury. We studied the involvement of ATP-sensitive potassium channel (KATP channel) in ischemic protection induced by these stimuli. Anesthetized rabbits were preconditioned with either HS (by raising temperature to 42 degrees C for 15 min) or intravenous pretreatment with MLA (35 micrograms/kg). After 24 h, animals were re-anesthetized and subjected to 30-min regional ischemia followed by 180-min reperfusion (I/R). KATP channel blockers glibenclamide and/or 5-hydroxydecanoate (5-HD) were used to inhibit channel function. The 72 kD heat shock protein (HSP-72) was measured by Western blots. HS produced a marked reduction in infarct size (39.4 +/- 8.1% to 14.3 +/- 2.5%, p < 0.05) that was abolished by glibenclamide (42.3 +/- 3.2%) and 5-HD (33.7 +/- 4.8%) when given before I/R. These drugs failed to block HS protection when given before HS. Expression of HSP-72 was increased in all HS groups as compared to non-HS groups in both glibenclamide and 5-HD-treated rabbits. Similarly, pretreatment with MLA reduced infarct size from 40 +/- 8.6% to 15.1 +/- 1.5% (p < 0.05). 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 HS and MLA exert their anti-ischemic effect through activation of KATP channel.
热休克（HS）和4-单磷酸脂A（MLA，一种内毒素的无毒类似物）可保护心肌免受缺血-再灌注损伤。我们研究了ATP敏感性钾通道（KATP通道）在这些刺激诱导的缺血保护中的作用。将麻醉的兔子用HS（通过将温度升至42℃持续15分钟）或静脉注射MLA（35微克/千克）进行预处理。24小时后，再次麻醉动物，使其经历30分钟的局部缺血，随后进行180分钟的再灌注（I/R）。使用KATP通道阻滞剂格列本脲和/或5-羟基癸酸（5-HD）抑制通道功能。通过蛋白质免疫印迹法测量72kD热休克蛋白（HSP-72）。HS使梗死面积显著减小（从39.4±8.1%降至14.3±2.5%，p<0.05），但在I/R前给予格列本脲（42.3±3.2%）和5-HD（33.7±4.8%）可消除这种作用。在HS前给予这些药物未能阻断HS的保护作用。在格列本脲和5-HD处理的兔子中，与非HS组相比，所有HS组中HSP-72的表达均增加。同样，MLA预处理使梗死面积从40±8.6%降至15.1±1.5%（p<0.05）。在MLA处理的兔子中，5-HD使梗死面积增加至51.9±5.8。在给予溶媒处理的对照兔子中，给予5-HD时梗死面积无显著改变。这些数据表明，HS和MLA通过激活KATP通道发挥其抗缺血作用。
