Preventive Effects of Exenatide on Endothelial Dysfunction Induced by Ischemia-Reperfusion Injury via KATP Channels
Preventive Effects of Exenatide on Endothelial Dysfunction Induced by Ischemia-Reperfusion Injury via KATP Channels
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DOI：
10.1161/atvbaha.110.222653
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发表时间：
2012-02-01
影响因子：
8.7
通讯作者：
Kim, Kwon Sam
中科院分区：
文献类型：
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作者：
Ha, Sang Jin;Kim, Weon;Kim, Kwon Sam
目的-本研究的目的是评估艾塞那肽给药是否可以预防缺血再灌注 (IR) 损伤引起的内皮依赖性血管舒张受损，以及这种作用是否由 K-ATP 通道开放介导。方法和结果-在双盲、安慰剂对照、交叉设计中，20 名志愿者被随机分配到 2 组：皮下艾塞那肽（10 μg）或安慰剂给药。在研究药物给药后 30 分钟，在 IR（肱动脉水平缺血 15 分钟，然后再灌注 15 分钟）损伤前后测量桡动脉的内皮依赖性血流介导扩张 (FMD)。 7天后，两组交叉接受另一种治疗（即安慰剂或艾塞那肽）并接受相同的方案。 IR 前桡动脉直径、FMD 和 IR 损伤后基线桡动脉直径在两组之间相似（P = 无显着差异）。服用安慰剂后，IR 显着减弱了 FMD（IR 前：12.0 +/- 6.23%；IR 后：4.6 +/- 3.57%，P = 0.02）。艾塞那肽预防了这种损害（IR前的FMD：15.0 +/- 7.14%；IR后的FMD：15.0 +/- 5.96%，P = 无显着差异；与安慰剂相比，P < 0.001）。在单独的方案中，这种保护作用通过用 K-ATP 通道阻滞剂格列本脲（格列本脲，5 mg）预处理完全消除（n = 7；IR 前 FMD：12.0 +/- 2.2%；IR 后：3.2 +/- 2.1%，P < 0.001）。结论 - 本研究表明，皮下注射艾塞那肽可保护 IR 诱导的内皮功能障碍通过在人类 IR 损伤模型中打开 K-ATP 通道。 （动脉硬化血栓 Vasc Biol.2012；32：474-480。）
Objective-The purpose of this study was to evaluate whether exenatide administration can prevent impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) injury and whether this effect is mediated by K-ATP channel opening.Methods and Results-In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groups: subcutaneous exenatide (10 mu g) or placebo administration. At 30 minutes after the study drug administration, endothelium-dependent flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion) injury. Seven days later, both groups were crossed over and received the other treatment (ie, placebo or exenatide) and underwent the same protocol. Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR injury were similar between 2 groups (P = no significant difference). After placebo administration, IR significantly blunted FMD (before IR: 12.0 +/- 6.23%; after IR: 4.6 +/- 3.57%, P = 0.02). Exenatide prevented this impairment (FMD before IR: 15.0 +/- 7.14%; FMD after IR: 15.0 +/- 5.96%, P = no significant difference; P < 0.001 compared with placebo). In a separate protocol, this protective effect was completely abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of K-ATP channels (n = 7; FMD before IR: 12.0 +/- 2.2%; after IR: 3.2 +/- 2.1%, P < 0.001).Conclusion-The present study demonstrates that subcutaneous exenatide protects IR-induced endothelial dysfunction through opening of K-ATP channels in human IR injury model. (Arterioscler Thromb Vasc Biol. 2012;32:474-480.)