Kristiansen Steen B, Solskov Lasse, Jessen Niels, Løfgren Bo, Schmitz Ole, Nielsen-Kudsk Jens Erik, Nielsen Torsten T, Bøtker Hans Erik, Lund Sten
Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Denmark.
Basic Clin Pharmacol Toxicol. 2009 Jul;105(1):10-6. doi: 10.1111/j.1742-7843.2009.00402.x. Epub 2009 Apr 8.
Late pre-conditioning protects against myocardial ischaemic-reperfusion injury. AMP-activated protein kinase (AMPK) is activated by exercise and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). Early pre-conditioning involves AMPK activation and increased myocardial glucose uptake. The aim of the present study was to determine whether AICAR activates myocardial AMPK and induces late pre-conditioning and whether myocardial glucose uptake during reperfusion was modulated. Twenty-four hours after AICAR treatment or exercise, Wistar rats were subjected to ischaemia and reperfusion in a Langendorff model and compared to control rats. AMPK activity increased immediately 2.5-fold in AICAR-treated animals (P < 0.01) and twofold in exercised animals (P < 0.05). AICAR and exercise reduced infarct size by 60% and 50% (both P < 0.01), respectively, and increased myocardial glucose uptake during reperfusion (AICAR; 45%, P < 0.05, exercise; 40%, P < 0.05). In conclusion, AICAR induces late pre-conditioning and increases myocardial glucose uptake during reperfusion in rat hearts. AICAR and exercise activate AMPK, suggesting a role of AMPK in the signalling mechanisms behind late pre-conditioning.
延迟预处理可保护心肌免受缺血再灌注损伤。AMP激活的蛋白激酶（AMPK）可被运动和5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）激活。早期预处理涉及AMPK激活和心肌葡萄糖摄取增加。本研究的目的是确定AICAR是否激活心肌AMPK并诱导延迟预处理，以及再灌注期间心肌葡萄糖摄取是否受到调节。在AICAR治疗或运动24小时后，将Wistar大鼠在Langendorff模型中进行缺血和再灌注，并与对照大鼠进行比较。在AICAR处理的动物中，AMPK活性立即增加2.5倍（P < 0.01），在运动的动物中增加2倍（P < 0.05）。AICAR和运动分别使梗死面积减少60%和50%（均P < 0.01），并增加再灌注期间的心肌葡萄糖摄取（AICAR；45%，P < 0.05，运动；40%，P < 0.05）。总之，AICAR可诱导大鼠心脏延迟预处理并增加再灌注期间的心肌葡萄糖摄取。AICAR和运动激活AMPK，提示AMPK在延迟预处理背后的信号传导机制中起作用。
