李泳洁,马海平,吴建江,杨龙,郭海,王江

• 1:新疆医科大学第一附属医院麻醉科

摘要(Abstract)：

目的探讨七氟醚后处理对抗心肌细胞缺氧/复氧(H/R)损伤过程中,缺氧诱导因子-1α/巨噬细胞移动抑制因子(HIF-1α/MIF)信号轴发挥的调控作用及相关作用机制。方法运用大鼠心肌细胞(H9C2)建立H/R损伤模型,分为空白对照组(NOR组)、缺氧/复氧组(H/R组)、七氟醚后处理组(SPostC组)、HIF-1α抑制剂组(YC-1组)。采用乳酸脱氢酶(LDH)及细胞计数试剂盒-8(CCK-8)检测细胞存活率;流式细胞仪检测细胞凋亡;活性氧(ROS)和腺嘌呤核苷三磷酸(ATP)试剂盒检测细胞能量代谢;通过Western blot检测HIF-1α、巨噬细胞移动抑制因子(MIF)、腺苷酸活化蛋白激酶α(AMPKα)和磷酸化AMPKα(p-AMPKα)的蛋白表达水平。结果 (1)与NOR组和H/R组相比,SPostC组显著上调了HIF-1α的表达、抑制细胞凋亡、减少ROS生成、增加ATP含量和减少LDH含量,经比较差异具有统计学意义(P<0.05);(2)与H/R组相比,SPostC组和YC-1组中HIF-1α的表达水平分别与MIF和AMPK的蛋白表达呈正相关(P<0.05);(3)与SPostC组相比,YC-1组抑制HIF-1α的表达,MIF、AMPKα和p-AMPKα呈低表达,经比较差异具有统计学意义(P<0.05)。结论七氟醚后处理通过上调HIF-1α/MIF信号轴对抗心肌细胞H/R损伤。

关键词(KeyWords)： 七氟醚后处理;心肌细胞缺氧/复氧;缺氧诱导因子-1α(HIF-1α);巨噬细胞移动抑制因子(MIF);腺苷酸活化蛋白激酶(AMPK)

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金（81760044）

作者(Author): 李泳洁,马海平,吴建江,杨龙,郭海,王江

参考文献(References)：

• [1]RASSAF T,WEBER C,BERNHAGEN J.Macrophage migration inhibitory factor in myocardial ischaemia/reperfusion injury[J].Cardiovasc Res,2014,102(2):321-328.
• [2]DONG J,XU M,ZHANG WY,et al.Effects of sevoflurane pretreatment on myocardial ischemia-reperfusion injury through the Akt/hypoxia-inducible factor 1-alpha (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway[J].Med Sci Monit,2019,25:3100-3107.
• [3]YANG L,XIE P,WU JJ,et al.Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1[J].Am J Transl Res,2016,8(10):4415-4424.
• [4]YANG L,XIE P,WU JJ,et al.Deferoxamine treatment combined with sevoflurane postconditioning attenuates myocardial ischemiareperfusion injury by restoring HIF-1/BNIP3-Mediated mitochondrial autophagy in GK rats[J].Front Pharmacol,2020,11:6.
• [5]JANKAUSKAS SS,WONG DWL,BUCALA R,et al.Evolving complexity of Mif signaling[J].Cell Signal,2019,57:76-88.
• [6]POHL J,HENDGEN-COTTA UB,STOCK P,et al.Myocardial expression of macrophage migration inhibitory factor in patients with heart failure[J].J Clin Med,2017,6(10):95.
• [7]YU J,MAIMAITILI Y,XIE P,et al.High glucose concentration abrogates sevoflurane post-conditioning cardioprotection by advancing mitochondrial fission but dynamin-related protein 1 inhibitor restores these effects[J].Acta Physiol (Oxf),2017,220(1):83-98.
• [8]吴建江,杨龙,太来提·台万古,等.上调HIF-1对老龄大鼠心肌线粒体功能的影响[J].新疆医科大学学报,2021,44(1):28-32.
• [9]LU S,DING Y,YU M,et al.Electroacupuncture for myocardial ischemia injury in rats via AMPK-HDAC5-HIF-1αsignaling[J].Zhongguo Zhen Jiu,2018,38(9):978-983.
• [10]BILSBORROW JB,DOHERTY E,TILSTAM PV,et al.Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus[J].Expert Opin Ther Targets,2019,23(9):733-744.
• [11]CALANDRA T,BUCALA R.Macrophage migration inhibitory factor (MIF):A glucocorticoid counter-regulator within the immune system[J].Crit Rev Immunol,2017,37(2-6):359-370.
• [12]FARR L,GHOSH S,MOONAH S.Role of MIF Cytokine/CD74 receptor pathway in protecting against injury and promoting repair[J].Front Immunol,2020,11:1273.
• [13]YU H,WANG X,DENG X,et al.Correlation between plasma macrophage migration inhibitory factor levels and long-term prognosis in patients with acute myocardial infarction complicated with diabetes[J].Mediators Inflamm,2019,2019:8276180.
• [14]RUZE A,CHEN BD,LIU F,et al.Macrophage migration inhibitory factor plays an essential role in ischemic preconditioning-mediated cardioprotection[J].Clin Sci (Lond),2019,133(5):665-680.
• [15]EMONTZPOHL C,STOPPE C,THEI?EN A,et al.The Role of Macrophage migration inhibitory factor in remote ischemic conditioning induced hepatoprotection in a rodent model of liver transplantation[J].Shock,2019,52(5):e124-e134.
• [16]YANG X,COHEN MV,DOWNEY JM.Mechanism of cardioprotection by early ischemic preconditioning[J].Cardiovasc Drugs Ther,2015,24:225-234.
• [17]DUAN X,JI B,YU K,et al.Pharmacological postconditioning protects isolated rat hearts against ischemia-reperfusion injury:the role of mitochondrial permeability transition pore[J].ASAIO J,2011,57(3):197-202.
• [18]KUNECKI M,P?AZAK W,PODOLEC P,et al.Effects of endogenous cardioprotective mechanisms on ischemia-reperfusion injury[J].Postepy Hig Med Dosw (Online),2017,71:20-31.
• [19]LU L,MA J,SUN M,et al.Melatonin ameliorates MI-induced cardiac remodeling and apoptosis through a JNK/p53-dependent mechanism in diabetes mellitus[J].Oxid Med Cell Longev,2020,2020:1535201.