Pim-1激酶在麻醉诱导和缺血预处理对抗心肌梗死中的差异作用。
Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction.
作者信息
Stumpner Jan, Redel Andreas, Kellermann Anna, Lotz Christopher A, Blomeyer Christoph A, Smul Thorsten M, Kehl Franz, Roewer Norbert, Lange Markus
机构信息
Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
出版信息
Anesthesiology. 2009 Dec;111(6):1257-64. doi: 10.1097/ALN.0b013e3181bdf9f4.
BACKGROUND
Ischemic preconditioning (IPC) and anesthetic-induced preconditioning against myocardial infarction are mediated via protein kinase B. Pim-1 kinase acts downstream of protein kinase B and was recently shown to regulate cardiomyocyte survival. The authors tested the hypothesis that IPC and anesthetic-induced preconditioning are mediated by Pim-1 kinase.
METHODS
Pentobarbital-anesthetized male C57Black/6 mice were subjected to 45 min of coronary artery occlusion and 3 h of reperfusion. Animals received no intervention, Pim-1 kinase inhibitor II (10 microg/g intraperitoneally), its vehicle dimethyl sulfoxide (10 microl/g intraperitoneally), or 1.0 minimum alveolar concentration desflurane alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). IPC was induced by three cycles of 5 min ischemia-reperfusion each, and animals received IPC either alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). Infarct size was determined with triphenyltetrazolium chloride, and area at risk was determined with Evans blue (Sigma-Aldrich, Taufkirchen, Germany). Protein expression of Pim-1 kinase, Bad, phospho-Bad, and cytosolic content of cytochrome c were measured using Western immunoblotting.
RESULTS
Infarct size in the control group was 47 + or - 2%. Pim-1 kinase inhibitor II (44 + or - 2%) had no effect on infarct size. Desflurane (17 + or - 3%) and IPC (19 + or - 2%) significantly reduced infarct size compared with control (both P < 0.05 vs. control). Blockade of Pim-1 kinase completely abrogated desflurane-induced preconditioning (43 + or - 3%), whereas IPC (35 + or - 3%) was blocked partially. Desflurane tended to reduce cytosolic content of cytochrome c, which was abrogated by Pim-1 kinase inhibitor II.
CONCLUSION
These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice.
背景
缺血预处理（IPC）和麻醉诱导的心肌梗死预处理是通过蛋白激酶B介导的。Pim-1激酶在蛋白激酶B下游起作用，最近研究表明其可调节心肌细胞存活。作者检验了IPC和麻醉诱导的预处理是由Pim-1激酶介导的这一假说。
方法
用戊巴比妥麻醉的雄性C57Black/6小鼠接受45分钟冠状动脉闭塞和3小时再灌注。动物未接受任何干预、腹腔注射Pim-1激酶抑制剂II（10微克/克）、其溶媒二甲基亚砜（腹腔注射10微升/克），或单独给予1.0最低肺泡浓度的地氟醚，或与Pim-1激酶抑制剂II（腹腔注射10微克/克）联合使用。IPC通过三个5分钟缺血-再灌注周期诱导，动物单独接受IPC或与Pim-1激酶抑制剂II（腹腔注射10微克/克）联合使用。用氯化三苯基四氮唑测定梗死面积，用伊文思蓝（德国陶夫基兴西格玛奥德里奇公司）测定危险区域面积。用蛋白质免疫印迹法测量Pim-1激酶、Bad、磷酸化Bad的蛋白表达以及细胞色素c的胞浆含量。
结果
对照组梗死面积为47±2%。Pim-1激酶抑制剂II（44±2%）对梗死面积无影响。与对照组相比，地氟醚（17±3%）和IPC（19±2%）显著减小梗死面积（两者与对照组相比P均<0.05）。阻断Pim-1激酶完全消除了地氟醚诱导的预处理（43±3%），而IPC（35±3%）被部分阻断。地氟醚倾向于降低细胞色素c的胞浆含量，这一作用被Pim-1激酶抑制剂II消除。
结论
这些数据表明，Pim-1激酶至少部分介导了地氟醚诱导的预处理以及小鼠心肌梗死的IPC。
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