Weber Nina C, Goletz Christine, Huhn Ragnar, Grueber Yvonne, Preckel Benedikt, Schlack Wolfgang, Ebel Dirk
Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
Eur J Pharmacol. 2008 Sep 11;592(1-3):48-54. doi: 10.1016/j.ejphar.2008.07.010. Epub 2008 Jul 11.
Preconditioning by volatile anaesthetics is blocked by hyperglycaemia. The regulation of mitogen-activated protein kinases during this effect has yet not been investigated. For infarct size measurements, anaesthetized rats were subjected to 25 min coronary artery occlusion followed by 120 min reperfusion. Control animals were not further treated. One group was preconditioned by two 5-min periods of desflurane inhalation (desflurane preconditioning, Des-preconditioning, 1MAC), each followed by 10-min washout. Four groups received glucose 50% in order to achieve blood glucose concentrations between 22.2 and 33.3 mM/l. Glucose infusion started 40 min before ischaemia (early hyperglycaemia, EH) and stopped with the onset of artery occlusion with (EH+Des-preconditioning) or without (EH) preconditioning. The other two groups received glucose during ischaemia (late hyperglycaemia, LH), again with (LH+Des-preconditioning) or without (LH) preconditioning. Additional hearts were excised for Western blot of mitogen-activated protein kinases. Infarct size was reduced from 51.7+/-9.0% in controls to 28.8+/-11.8% after Des-preconditioning (P<0.01 vs Con). Hyperglycaemia alone did not affect infarct size (EH, 51.5+/-9.0%, LH, 44.3+/-16.9%), but EH as well as LH blocked Des-preconditioning (49.1+/-12.3%, P<0.01, 48.1+/-17.6%, P<0.05 vs Des-preconditioning). All three mitogen-activated protein kinases showed a similar time course pattern of phosphorylation in the Des-preconditioning, EH and EH+Des-preconditioning group. Despite the lack of cardioprotection, mitogen-activated protein kinases are activated in hyperglycaemic myocardium. Therefore, it can be assumed that the hyperglycaemic induced blockade of Des-preconditioning is situated downstream or in parallel of these mitogen-activated protein kinases or involves different signal transduction pathways.
挥发性麻醉剂预处理可被高血糖阻断。在此效应过程中丝裂原活化蛋白激酶的调节尚未得到研究。为测量梗死面积，将麻醉大鼠冠状动脉闭塞25分钟，随后再灌注120分钟。对照动物未作进一步处理。一组通过两次5分钟的地氟醚吸入进行预处理（地氟醚预处理，Des预处理，1MAC），每次吸入后冲洗10分钟。四组给予50%葡萄糖以使血糖浓度达到22.2至33.3 mM/l。葡萄糖输注在缺血前40分钟开始（早期高血糖，EH），并在动脉闭塞开始时停止，其中一组伴有（EH + Des预处理），另一组不伴有（EH）预处理。另外两组在缺血期间给予葡萄糖（晚期高血糖，LH），同样一组伴有（LH + Des预处理），另一组不伴有（LH）预处理。额外取出心脏用于丝裂原活化蛋白激酶的蛋白质印迹分析。梗死面积从对照组的51.7±9.0%降至Des预处理后的28.8±11.8%（与对照组相比，P<0.01）。单独高血糖不影响梗死面积（EH为51.5±9.0%，LH为44.3±16.9%），但EH和LH均阻断了Des预处理（分别为49.1±12.3%，P<0.01；48.1±17.6%，与Des预处理相比，P<0.05）。在Des预处理组、EH组和EH + Des预处理组中，所有三种丝裂原活化蛋白激酶均呈现相似的磷酸化时间进程模式。尽管缺乏心脏保护作用，但丝裂原活化蛋白激酶在高血糖心肌中被激活。因此，可以推测高血糖诱导的Des预处理阻断位于这些丝裂原活化蛋白激酶的下游或与之平行，或者涉及不同的信号转导途径。
