侯倩,王园园,赵志芳,胡海娟,崔炜

• 1:河北医科大学第二医院 河北省心血管研究所心内一科

摘要(Abstract)：

目的观察负荷剂量氟伐他汀预处理对在体大鼠心肌缺血再灌注损伤的保护作用。方法 84只大鼠随机分为12组,每组7只。其中氟伐他汀组(F-1~F-8组)分别于冠状动脉缺血前1、2、4、6、12、24、48和72 h灌胃氟伐他汀80 mg/kg;假手术组(Sham组)、缺血再灌注组(I/R组)、缺血预适应第一窗口组(IPC-1组)及第二窗口组(IPC-2组)灌胃等量生理盐水。建立大鼠心肌缺血再灌注损伤模型、缺血预适应保护模型及延迟保护模型。记录大鼠心律失常及心肌缺血、心肌梗死情况,测定血清乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性,光学显微镜及透射电镜下观察受损心肌细胞形态。结果氟伐他汀预处理组中,除F-5、F-6组外,其他组心肌梗死面积均较I/R组减小(P<0.05);负荷剂量氟伐他汀的保护作用呈现两个窗口,F-3、F-7组分别为其保护作用的最佳组(与I/R组比较,P<0.05);与IPC-1组比较,F-3组心肌缺血、心肌梗死程度、血清LDH和CK-MB均显著增高(P<0.05),心律失常评分差异无统计学意义(P>0.05)。与IPC-2组比较,F-7组梗死面积有减少趋势(P>0.05),心肌梗死质量显著降低(P<0.05),缺血程度显著增高(P<0.05)。结论负荷量氟伐他汀预处理对在体大鼠心肌缺血再灌注损伤的保护作用存在两个窗口,第一窗口较缺血预适应弱,第二窗口在减轻心肌梗死程度上有强于缺血预适应的趋势。

关键词(KeyWords)： 缺血再灌注损伤;缺血预适应;氟伐他汀;第二窗口保护

Abstract:

Keywords:

基金项目(Foundation): 河北省高等学校科学技术研究项目(20110202)

作者(Author): 侯倩,王园园,赵志芳,胡海娟,崔炜

参考文献(References)：

• [1]Thuc LC,Teshima Y,Takahashi N,et al.Cardioprotective effects of pravastatin against lethal ventricular arrhythmias induced by reperfusion in the rat heart.Circ J,2011,75:1601-1608.
• [2]Mensah K,Mocanu MM,Yellon DM.Failure to protect the myocardium against ischemia/reperfusion injury after chronic atorvastatin treatment is recaptured by acute atorvastatin treatment:a potential role for phosphatase and tensin homolog deleted on chromosome ten.J Am Coll Cardiol,2005,45:1287-1291.
• [3]ˇCarnickáS,AdameováA,NemˇcekováM,et al.Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning,arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.Physiol Res,2011,60:825-830.
• [4]Andreadou I,Farmakis D,Prokovas E,et al.Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning:effects on infarct size,endothelial nitric oxide synthase,and nitro-oxidative stress.Cardiovasc Res,2012,94:501-509.
• [5]Post S,Post MC,van den Branden BJ,et al.Early statin treatment prior to primary PCI for acute myocardial infarction:REPERATOR,a randomized placebo-controlled pilot trial.Catheter Cardiovasc Interv,2012,80:756-765.
• [6]Walker MJ,Curtis MJ,Hearse DJ,et al.The Lambeth Conventions:guidelines for the study of arrhythmias in ischaemia infarction,and reperfusion.Cardiovasc Res,1988,22:447-455.
• [7]Curtis MJ,Walker MJ.Quantification of arrhythmias using scoring systems:an examination of seven scores in an in vivo model of regional myocardial ischaemia.Cardiovasc Res,1988,22:656-665.
• [8]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation,1986,74:1124-1136.
• [9]Guo Y,Wu WJ,Qiu Y,et al.Demonstration of an early and a late phase of ischemic preconditioning in mice.Am J Physiol,1998,275:H1375-H1387.
• [10]Parratt JR.Protection of the heart by ischaemic preconditioning:mechanisms and possibilities for pharmacological exploitation.Trends Pharmacol Sci,1994,15:19-25.
• [11]Urbich C,Dernbach E,Zeiher AM,et al.Double-edged role of statins in angiogenesis signaling.Circ Res,2002,90:737-744.
• [12]Atar S,Ye Y,Lin Y,et al.Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2.Am J Physiol Heart Circ Physiol,2006,290:H1960-H1968.
• [13]Xuan YT,Guo Y,Zhu Y,et al.Mechanism of cyclooxygenase-2upregulation in late preconditioning.J Mol Cell Cardiol,2003,35:525-537.
• [14]Chen L,Lizano P,Zhao X,et al.Preemptive conditioning of the swine heart by H11 kinase/Hsp22 provides cardiac protection through inducible nitric oxide synthase.Am J Physiol Heart Circ Physiol,2011,300:H1303-H1310.
• [15]Zhao X,Park J,Ho D,et al.Cardiomyocyte overexpression of theα1A-adrenergic receptor in the rat phenocopies second but not fi rst window preconditioning.Am J Physiol Heart Circ Physiol,2012,302:H1614-H1624.
• [16]Thuc LC,Teshima Y,Takahashi N,et al.Mitochondrial K(ATP)channels-derived reactive oxygen species activate prosurvival pathway in pravastatin-induced cardioprotection.Apoptosis,2010,15:669-678.
• [17]Ye Y,Martinez JD,Perez-Polo RJ,et al.The role of e NOS,i NOS and NF-kappa B in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin.Am J Physiol Heart Circ Physiol,2008,295:H343-H351.