Kansal Sunil Kumar, Jyoti Uma, Sharma Samridhi, Kaura Arun, Deshmukh Rahul, Goyal Sandeep
University Institute of Pharmaceutical Sciences & Research, Baba Farid University of Health Sciences, Faridkot, Punjab, 151203, India.
Naunyn Schmiedebergs Arch Pharmacol. 2015 Jun;388(6):635-41. doi: 10.1007/s00210-015-1105-6. Epub 2015 Mar 7.
Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.
高脂血症被视为缺血性心脏病发展中的独立危险因素，它会增加心肌对缺血/再灌注（I/R）诱导损伤的易感性。高脂血症会减弱缺血预处理（IPC）的心脏保护反应。本研究调查了补锌对高脂血症大鼠心脏缺血预处理减弱的心脏保护作用的影响。通过喂食高脂饮食（HFD）6周诱导大鼠高脂血症，然后观察血清脂质谱。在实验中，将离体的Langendorff大鼠心脏标本进行4个周期的缺血预处理（IPC），然后缺血30分钟，再灌注120分钟。通过氯化三苯基四氮唑（TTC）染色从形态学上阐述心肌梗死面积，并通过乳酸脱氢酶（LDH）和肌酸激酶-MB（CK-MB）从冠状动脉流出液中的释放以及左心室胶原蛋白含量进行生化分析。然而，补锌的效果，即在再灌注期间灌注120分钟的吡啶硫酮锌（10μM），显著消除了高脂血症大鼠心脏中缺血预处理减弱的心脏保护作用，而在灌注吡啶硫酮锌前2分钟再灌注期间给予这种锌离子载体的螯合剂，即N,N,N',N'-四（2-吡啶甲基）乙二胺（TPEN；10μM），消除了高脂血症大鼠心脏实验中补锌的心脏保护作用。因此，补锌可限制梗死面积、LDH和CK-MB，并提高胶原蛋白水平，这表明高脂血症大鼠中IPC减弱的心脏保护作用是由于缺血/再灌注导致再灌注期间锌流失所致。
