Qian Y Z, Levasseur J E, Yoshida K, Kukreja R C
Eric Lipman Laboratories of Molecular and Cellular Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):H23-8. doi: 10.1152/ajpheart.1996.271.1.H23.
The objective of this study was to examine if the opening of ATP-sensitive K+ (KATP) channels play an important role in ischemic preconditioning (PC) in the rat heart. A second goal was to test the role of acetylcholine (ACh) in mimicking PC and test if it could be blocked by KATP antagonist. Glibenclamide, a specific antagonist of the KATP channel, was given as two doses of 0.3 mg/kg each at 60 and 30 min before PC. Six groups of rats were subjected to ischemia and reperfusion (I/R) using these protocols: 1) control (I/R), 30-min ischemia followed by 90-min reperfusion (n = 6 rats); 2) preconditioned hearts given 5-min ischemia 10 min before I/R (n = 9 rats); 3) glibenclamide (0.3 mg/kg) treatment 60 and 30 min before PC (n = 13 rats); 4) glibenclamide treatment before I/R (n = 15 rats); 5) ACh infusion for 5 min (18 micrograms/ml) at a rate of 0.15 ml/min followed by equilibration for 10 min before I/R, n = 13 rats; and 6) glibenclamide treatment before ACh infusion followed by I/R (n = 11 rats). Preconditioning reduced the infarcted area (expressed as percent area at risk) from 42.0 +/- 4.4% in control to 8.7 +/- 6% (mean +/- SE, P < 0.05). Glibenclamide blocked the protection conferred by PC (39.1 +/- 4.5%, P < 0.05) without having a significant effect on control nonpreconditioned hearts. ACh infusion in lieu of PC also reduced infarct size to 25.0 +/- 5.63% (P < 0.05 compared with control), which was again blocked by glibenclamide (44.2 +/- 5.0%, P < 0.05). The data suggest that opening of KATP channels for ischemic and ACh-mediated preconditioning is also important in the rat heart.
本研究的目的是检验ATP敏感性钾离子（KATP）通道的开放在大鼠心脏缺血预处理（PC）中是否发挥重要作用。第二个目标是测试乙酰胆碱（ACh）在模拟PC中的作用，并测试其是否能被KATP拮抗剂阻断。格列本脲是KATP通道的特异性拮抗剂，在PC前60分钟和30分钟各给予0.3 mg/kg两剂。使用这些方案对六组大鼠进行缺血再灌注（I/R）：1）对照组（I/R），30分钟缺血后90分钟再灌注（n = 6只大鼠）；2）在I/R前10分钟给予5分钟缺血预处理的心脏（n = 9只大鼠）；3）在PC前60分钟和30分钟给予格列本脲（0.3 mg/kg）治疗（n = 13只大鼠）；4）在I/R前给予格列本脲治疗（n = 15只大鼠）；5）在I/R前以0.15 ml/min的速率输注ACh 5分钟（18微克/毫升），随后平衡10分钟，n = 13只大鼠；6）在输注ACh前给予格列本脲治疗，随后进行I/R（n = 11只大鼠）。预处理将梗死面积（以危险区域面积百分比表示）从对照组的42.0±4.4%降至8.7±6%（平均值±标准误，P<0.05）。格列本脲阻断了PC所赋予的保护作用（39.1±4.5%，P<0.05），而对未预处理的对照心脏无显著影响。输注ACh代替PC也将梗死面积减小至25.0±5.63%（与对照组相比P<0.05），这同样被格列本脲阻断（44.2±5.0%，P<0.05）。数据表明，KATP通道的开放对缺血和ACh介导的预处理在大鼠心脏中也很重要。
