Weber N C, Stursberg J, Wirthle N M, Toma O, Schlack W, Preckel B
Department of Anaesthesiology, University Hospital of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Br J Anaesth. 2006 Sep;97(3):298-306. doi: 10.1093/bja/ael153. Epub 2006 Jun 21.
Xenon (Xe) induces preconditioning (PC) of the rat heart in vivo via activation of p38 mitogen-activated protein kinase (MAPK). The role of ERK 1/2 and JNK 1/2 and 3 in Xe-PC has yet not been determined.
For infarct size measurements, anaesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Animals received Xe 70% during three 5 min periods with and without the ERK inhibitor PD 98059 (1 mg kg(-1), PD) or the JNK inhibitor SP 600125 (6 mg kg(-1), SP) (n=10 per group). Additional hearts were excised for western blot and kinase activity assay: without further treatment, after the first, the second and the third period of Xe-PC or at the end of the last washout phase (n=4 each).
Infarct size (% of area at risk) was reduced from 46.2 (8.1)% to 28.4 (11.3)% after Xe-PC (P<0.01). PD completely abolished this effect [49.7 (11.4)%, P<0.01 vs Xe-PC]. The ratio of particulate/cytosolic phospho ERK 1/2 was time dependently increased during the PC protocol [ERK 1: 15 min: 2.4 (1.2), 25 min: 1.5 (0.3), 35 min: 1.6 (0.7), 45 min: 1.5 (0.5) vs Con 1.0 (0.5) and ERK 2: 15 min: 3.3 (1.8), 25 min: 2.0 (1.5), 35 min: 1.8 (1.7), 45 min: 0.9 (0.6) vs Con 0.8 (0.4)]. This finding was confirmed by a non-radioactive MAPK activity assay. In contrast SP had no effect on Xe-PC and the phosphorylation state of JNK was not influenced by Xe-PC.
Besides the p38 MAPK, ERK 1/2 also is a mediator of Xe-PC. However, JNK is not involved, demonstrating a highly specific regulation of different kinases during Xe-PC.
氙气（Xe）通过激活p38丝裂原活化蛋白激酶（MAPK）在体内诱导大鼠心脏产生预处理（PC）。然而，细胞外信号调节激酶1/2（ERK 1/2）以及c-Jun氨基末端激酶1/2和3（JNK 1/2和3）在Xe-PC中的作用尚未明确。
为测量梗死面积，将麻醉后的大鼠进行25分钟冠状动脉闭塞，随后再灌注120分钟。在有或没有ERK抑制剂PD 98059（1 mg·kg⁻¹，PD）或JNK抑制剂SP 600125（6 mg·kg⁻¹，SP）的情况下，动物在三个5分钟时间段内吸入70%的Xe（每组n = 10）。另外切除心脏用于蛋白质免疫印迹和激酶活性测定：未进行进一步处理、在Xe-PC的第一个、第二个和第三个时间段后或在最后洗脱阶段结束时（每组n = 4）。
Xe-PC后梗死面积（危险区域面积的百分比）从46.2（8.1）%降至28.4（11.3）%（P < 0.01）。PD完全消除了这种作用[49.7（11.4）%，与Xe-PC相比P < 0.01]。在PC方案期间，颗粒状/胞质磷酸化ERK 1/2的比例呈时间依赖性增加[ERK 1：15分钟：2.4（1.2），25分钟：1.5（0.3），35分钟：1.6（0.7），45分钟：1.5（0.5），而对照组为1.0（0.5）；ERK 2：15分钟：3.3（1.8），25分钟：2.0（1.5），35分钟：1.8（1.7），45分钟：0.9（0.6），而对照组为0.8（0.4）]。这一发现通过非放射性MAPK活性测定得到证实。相比之下，SP对Xe-PC没有影响，且Xe-PC不影响JNK的磷酸化状态。
除p38 MAPK外，ERK 1/2也是Xe-PC的介质。然而，JNK不参与其中，这表明在Xe-PC过程中不同激酶存在高度特异性的调节。
