摘要
采用Langendorff离体灌流装置,通过停灌40min/复灌30min复制大鼠心肌缺血/再灌注(ischemia/reperfusion,IR)损伤模型,观察11,12-环氧二十碳三烯酸(11,12-epoxyeicosatrienoic acid,11,12-EET)预处理和后处理对心肌线粒体功能以及心功能的影响,探讨11,12-EET预处理和后处理对IR大鼠心肌的作用及其机制。将30只Sprague-Dawley大鼠随机分为对照组、IR组、EET预处理组(Pre-EET)、EET后处理组(Post-EET),每组6只。除对照组外,其它各组全心缺血40min,再灌注30min。监测左心室内压差(ΔLVP)和左心室内压升降的最大变化率(±dp/dtmax)等心功能指标,测定灌流液中乳酸脱氢酶(lactate dehydrogenase,LDH)的活性。灌流结束后,测定心肌线粒体琥珀酸脱氢酶(succinate dehydrogenase,SDH)、Ca2+-ATPase、Na+-K+-ATPase活性以及心肌超氧化物歧化酶(superoxide dismutase,SOD)活性、丙二醛(malon dialdehyde,MDA)含量。结果显示:(1)与IR组相比,Pre-EET组及Post-EET组Na+-K+-ATPase和SDH活性均增强,Ca2+-ATPase活性均减弱,有显著性差异(P<0.05);而Pre-EET与Post-EET组间没有显著性差异。(2)与IR组相比,Pre-EET组及Post-EET组心功能明显改善,LDH漏出显著减少,心肌SOD活性明显增强,MDA含量明显降低,有显著性差异(P<0.05);而Pre-EET与Post-EET组间没有显著性差异。结果表明,11,12-EET预处理及后处理均可通过上调心肌线粒体Na+-K+-ATPase、SDH活性以及下调Ca2+-ATPase活性改善线粒体功能和心肌能量代谢,拮抗心肌IR损伤;11,12-EET预处理及后处理还可通过提高心肌SOD活性、降低MDA含量改善IR心肌的氧化应激。
To explore the effects of 11,12-epoxyeicosatrienoic acid （11,12-EET） preconditioning and postconditioning on myocardial ischemia/reperfusion （IR） injury in rats, the IR injury model was built by stopping perfusion for 40 min followed by reperfusion for 30 min, and the changes of mitochondrial functions, myocardial metabolism and function were measured. Langendorff-perfused isolated rat hearts were divided into 4 groups： control group, persistently perfused with Krebs-Henseleit （K-H） fluid for 100 min; IR group, stopped perfusion for 40 rain followed by reperfusion for 30 min; Pre-EET group, preconditioned with 6.24× 10^-9 mol/L 11,12-EET for 5 rain twice before subjected to ischemia; Post-EET group, postconditioned with 6.24×10^-9 mol/L 11,12-EET for 30 s twice before reperfusion. The computer-based electrophysiological recording system was used to measure the changes of maximal rate of the pressure increase in contract phase （＋dp/dtmax）, maximal rate of the pressure decrease in diastole phase of heart （-dp/dtmax）, left ventricular end-diastolic pressure （LVEDP） and difference of left ventricular pressure （ALVP）. The activities of lactate dehydrogenase （LDH） in effluent, Ca^2＋-ATPase, Na^＋-K^＋-ATPase and succinate dehydrogenase （SDH） in mitochondria were measured with colorimetry method; superoxide dismutase （SOD） activity was measured with hydroxylamine method and malondialdehyde （MDA） content in myocardial tissues was measured with TBA method. The results showed that： （1） Compared with that in the control group, the myocardial functions, the values of SOD, SDH and Na^＋-K^＋-ATPase were decreased in IR group （P〈0.05）; the values of LDH, MDA and Ca^2＋-ATPase were increased （P〈0.05） in IR group. （2） Compared with that in IR group, the values of SDH and Na^＋K^＋-ATPase were increased （P〈 0.05） and the value of Ca^2＋-ATPase was decreased （P〈0.05） in both Pre-EET and Post-EET groups. But no significant differences were
出处
《生理学报》
CAS
CSCD
北大核心
2008年第1期23-28,共6页
Acta Physiologica Sinica
基金
supported by the Educational Science Foundation of Beijing (No. KM200510025009, KM200710025004)
theNational Basic Research Development Program of China (No. 2006CB503807)
