Ghyasi Rafigheh, Sepehri Gholamreza, Mohammadi Mustafa, Badalzadeh Reza, Ghyasi Akbar
Applied Drug Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
J Res Med Sci. 2012 Dec;17(12):1150-5.
Myocardial infarction (MI) is the acute condition of necrosis in myocardium which occurs as a result of imbalance between coronary blood supply and myocardial demand. The resultant oxidative stress excess leads to worsen the condition. The aim of this study was to investigate the effect of mebudipine, a new dihydropyridine calcium channel blocker, on lipid peroxidation and antioxidant enzymes in myocardial ischemia-reperfusion injury.
Male Wistar rats (250-300 g) were randomly divided to Control-ischemic, mebudipine-ischemic and vehicle (ethanol-ischemic) groups. The hearts of anaesthetized rats were removed and mounted on Langendorff apparatus and perfused by Krebs-Henseleit solution under constant pressure of 75 mmHg at 37°C. Ischemic groups were received 30 min global ischemia and 120 min reperfusion and the mebudipine and vehicle groups received mebudipine (0.1 nM) or ethanol (0.01%)-enriched solution 25 min before global ischemia. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase levels of heart tissue samples were determined by commercial specific Kits.
Mebudipine significantly reduced the MDA level (2.3 ± 0.07 nmol/mg protein) as the biochemical indicator of oxidative damage and lipid peroxidation product as compared with those of vehicle (4.6 ± 0.01 nmol/mg protein) and control groups (4.8 ± 0.09 nmol/mg protein). Furthermore, antioxidant enzymes SOD (0.1 ± 0.006 in drug vs. 0.037 ± 0.009 U/mg Protein in control), GPX (16 ± 0.009 in drug vs. 0.068 ± 0.01 U/mg Protein in control) and catalase activities (0.075 ± 0.006 in drug vs. 0.028 ± 0.002 U/mg Protein in control), activities of myocardium were significantly increased by mebudipine (P < 0.01).
Our results showed that mebudipine may have antioxidant activity against myocardial ischemia-reperfusion injury since it decreased oxidative stress by enhancing the enzymatic antioxidant defense and inhibiting the lipid peroxidation. Thus, this drug can reduce the intensity of cardiac ischemic insults.
心肌梗死（MI）是由于冠状动脉供血与心肌需求失衡导致的心肌急性坏死状态。由此产生的氧化应激过盛会使病情恶化。本研究旨在探讨新型二氢吡啶类钙通道阻滞剂美布地尔对心肌缺血再灌注损伤中脂质过氧化和抗氧化酶的影响。
将雄性Wistar大鼠（250 - 300 g）随机分为对照组-缺血组、美布地尔-缺血组和溶剂组（乙醇-缺血组）。将麻醉大鼠的心脏取出，安装在Langendorff装置上，在37℃、75 mmHg恒压下用Krebs-Henseleit溶液灌注。缺血组接受30分钟全心缺血和120分钟再灌注，美布地尔组和溶剂组在全心缺血前25分钟接受美布地尔（0.1 nM）或富含乙醇（0.01%）的溶液。心脏组织样本中的丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPX）和过氧化氢酶水平通过商业专用试剂盒测定。
与溶剂组（4.6±0.01 nmol/mg蛋白质）和对照组（4.8±0.09 nmol/mg蛋白质）相比，美布地尔显著降低了作为氧化损伤和脂质过氧化产物生化指标的MDA水平（2.3±0.07 nmol/mg蛋白质）。此外，美布地尔使心肌中抗氧化酶SOD（药物组为0.1±0.006，对照组为0.037±0.009 U/mg蛋白质）、GPX（药物组为16±0.009，对照组为0.068±0.01 U/mg蛋白质）和过氧化氢酶活性（药物组为0.075±0.006，对照组为0.028±0.002 U/mg蛋白质）显著增加（P<0.01）。
我们的结果表明，美布地尔可能对心肌缺血再灌注损伤具有抗氧化活性，因为它通过增强酶促抗氧化防御和抑制脂质过氧化来降低氧化应激。因此，这种药物可以减轻心脏缺血损伤的强度。
