Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
Acta Anaesthesiol Scand. 2012 Aug;56(7):904-13. doi: 10.1111/j.1399-6576.2012.02657.x. Epub 2012 Mar 5.
Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase.
Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10 μg/g intraperitoneally) or its vehicle dimethy sulfoxide (10 μl/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18 min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-Bad(Ser112) and B-cell lymphoma 2 was determined using Western immunoblotting analysis.
Infarct size in control animals (CON) was 46 ± 3%. Dimethylsulfoxide (47 ± 3%) and Pim-1 kinase inhibitor II (44 ± 5%) did not significantly reduce infarct size. Desflurane (16 ± 2%*; P < 0.05 vs. CON) and IPOST (21 ± 2%) significantly reduced infarct size compared with CON. Inhibition of Pim-1 kinase abolished desflurane-induced postconditioning (46 ± 4%) and IPOST (44 ± 5%). Western blot analysis revealed that only desflurane enhances phosphorylation of Bad at serine 112 that was abrogated by Pim-1 kinase inhibitor II.
These data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.
麻醉诱导（APOST）和缺血后处理（IPOST）对心肌梗死的保护作用是通过磷脂酰肌醇-3-激酶/蛋白激酶 B（Akt）介导的。Pim-1 激酶位于 Akt 的下游，最近已被证明能增强心肌细胞的存活。我们检验了这样一个假设，即 APOST 和 IPOST 都是由 Pim-1 激酶介导的。
戊巴比妥钠麻醉雄性 C57BL/6 小鼠，进行 45 分钟的冠状动脉闭塞（CAO）和 3 小时的再灌注。动物接受了以下干预：不干预、Pim-1 激酶抑制剂 II（10μg/g 腹腔内注射）或其载体二甲亚砜（10μl/g 腹腔内注射）。在 CAO 结束前 3 分钟，给予 1.0 最低肺泡浓度的地氟醚 18 分钟，单独或与 Pim-1 激酶抑制剂 II 联合使用。通过每个 10 秒缺血/再灌注的 3 个循环诱导 IPOST，动物接受 IPOST 单独或与 Pim-1 激酶抑制剂 II 联合使用。用三苯基四氮唑氯化物测定梗死面积，用 Evans 蓝测定危险区面积。使用 Western 免疫印迹分析测定 Pim-1 激酶、Bad、磷酸化 Bad（Ser112）和 B 细胞淋巴瘤 2 的蛋白表达。
对照组（CON）的梗死面积为 46±3%。二甲亚砜（47±3%）和 Pim-1 激酶抑制剂 II（44±5%）并没有显著减少梗死面积。地氟醚（16±2%*；P<0.05 与 CON 相比）和 IPOST（21±2%）与 CON 相比显著减少了梗死面积。Pim-1 激酶抑制剂的抑制作用消除了地氟醚诱导的后处理（46±4%）和 IPOST（44±5%）。Western blot 分析显示，只有地氟醚增强了 Bad 在丝氨酸 112 处的磷酸化，而 Pim-1 激酶抑制剂 II 则消除了这种磷酸化。
这些数据表明，Pim-1 激酶介导了地氟醚诱导的后处理和 IPOST 在小鼠中的作用。
