Pim-1 Kinase Regulating Dynamics Related Protein 1 Mediates Sevoflurane Postconditioning-induced Cardioprotection  

作　　者：Jin-Dong Liu Hui-Juan Chen Da-Liang Wang Hui Wang Qian Deng 

机构地区：[1]Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China [2]Department of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China

出　　处：《Chinese Medical Journal》2017年第3期309-317,共9页中华医学杂志（英文版）

摘　　要：Background： It is well documented that sevoflurane postconditioning （SP） has a significant myocardial protection effect. However, the mechanisms underlying SP are still unclear. In the present study, we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 （Drpl）. Methods： A Langendorff model was used in this study. Seventy-two rats were randomly assigned into six groups as follows： CON group, ischemia reperfusion （I/R） group, SP group, SP＋proto-oncogene serine/threonine-protein kinase 1 （Pim-1） inhibitor II group, SP＋dimethylsufoxide group, and Pim- 1 inhibitor II group （n = 12, each）. Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial 1/R injury. The expressions ofPim-1, B-cell leukemia/lymphoma 2 （Bcl-2） and cytochrome C （Cyt C） in cytoplasm and mitochondria, the Drp 1 in mitochondria, and the total Drp I and p-Drp I^sor637 were measured by Western blotting. In addition, transmission electron microscope was used to observe mitochondrial morphology. The experiment began in October 2014 and continued until July 2016. Results： SP improved myocardial I/R injury-induced hemodynamic parametric changes, cardiac function, and preserved mitochondrial phenotype and decreased myocardial infarct size （24.49 ± 1.72% in Sev group compared with 41.98 ± 4.37% in I/R group; P 〈 0.05）. However, Pim-1 inhibitor II significantly （P 〈 0.05） abolished the protective effect of SP. Western blotting analysis demonstrated that, compared with I/R group, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drplset637 in Sev group （P 〈 0.05） were upregulated. Meanwhile, SP inhibited Drp 1 compartmentalization to the mitochondria followed by a reduction in the release ofCyt C. Pretreatment with Pim- 1 inhibitor II significantly （P 〈 0.05） abolished SP-induced Pim- 1/p-Drp 1^ser637 signaling activation. Conclusions： TBackground： It is well documented that sevoflurane postconditioning （SP） has a significant myocardial protection effect. However, the mechanisms underlying SP are still unclear. In the present study, we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 （Drpl）. Methods： A Langendorff model was used in this study. Seventy-two rats were randomly assigned into six groups as follows： CON group, ischemia reperfusion （I/R） group, SP group, SP＋proto-oncogene serine/threonine-protein kinase 1 （Pim-1） inhibitor II group, SP＋dimethylsufoxide group, and Pim- 1 inhibitor II group （n = 12, each）. Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial 1/R injury. The expressions ofPim-1, B-cell leukemia/lymphoma 2 （Bcl-2） and cytochrome C （Cyt C） in cytoplasm and mitochondria, the Drp 1 in mitochondria, and the total Drp I and p-Drp I^sor637 were measured by Western blotting. In addition, transmission electron microscope was used to observe mitochondrial morphology. The experiment began in October 2014 and continued until July 2016. Results： SP improved myocardial I/R injury-induced hemodynamic parametric changes, cardiac function, and preserved mitochondrial phenotype and decreased myocardial infarct size （24.49 ± 1.72% in Sev group compared with 41.98 ± 4.37% in I/R group; P 〈 0.05）. However, Pim-1 inhibitor II significantly （P 〈 0.05） abolished the protective effect of SP. Western blotting analysis demonstrated that, compared with I/R group, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drplset637 in Sev group （P 〈 0.05） were upregulated. Meanwhile, SP inhibited Drp 1 compartmentalization to the mitochondria followed by a reduction in the release ofCyt C. Pretreatment with Pim- 1 inhibitor II significantly （P 〈 0.05） abolished SP-induced Pim- 1/p-Drp 1^ser637 signaling activation. Conclusions： T

关 键 词：CARDIOPROTECTION Ischemia-reperfusion Injury MITOCHONDRIA PIM-1 POSTCONDITIONING SEVOFLURANE 

分 类 号：Q55[生物学—生物化学] Q813.3