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催产素对麻醉大鼠心肌缺血/再灌注损伤的双相保护作用。

Biphasic protective effect of oxytocin on cardiac ischemia/reperfusion injury in anaesthetized rats.

机构信息

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.

出版信息

Peptides. 2009 Dec;30(12):2301-8. doi: 10.1016/j.peptides.2009.09.010. Epub 2009 Sep 15.

DOI:10.1016/j.peptides.2009.09.010
PMID:19761809
Abstract

Oxytocin (OT) is well known for its role in reproduction. However, evidence has emerged suggesting a role in cardiovascular system. The aim of this study was to investigate the cardioprotective effect of oxytocin on ischemia/reperfusion (I/R) injury in an in vivo rat. Myocardial ischemia, was surgically induced by means of left anterior descending coronary artery occlusion for 25 min followed by reperfusion for 120 min. Infarct size was evaluated using the staining agent 2,3,5-triphenyltetrazolium chloride. Creatine kinase-MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH) levels in plasma were analyzed to assess the degree of cardiac injury. Intraperitoneal administration of OT 0.001, 0.01 and 0.1 microg significantly reduced infarct size, LDH and CK-MB levels as compared to control (I/R) group and it had a biphasic effect on the reduction of ischemia/reperfusion injury. This biphasic effect was revealed as a U-shaped curve in which efficacy was optimal between very low and very high doses. Furthermore there were no significant differences in mean arterial pressure or heart rate between the OT treatment groups and control group during I/R. Blockade of specific OT receptors by atosiban (10(-6)M) abolished or attenuated the effect of OT preconditioning. The result of this study shows that OT possess a dose-dependent cardioprotective effect against ischemia/reperfusion injury and so study of OT preconditioning may provide a new target site for therapeutic exploitation.

摘要

催产素(OT)以其在生殖系统中的作用而闻名。然而,有证据表明它在心血管系统中也有作用。本研究旨在研究催产素对体内大鼠缺血/再灌注(I/R)损伤的心脏保护作用。心肌缺血通过左前降支冠状动脉闭塞 25 分钟,然后再灌注 120 分钟来诱导。使用 2,3,5-三苯基氯化四唑染料评估梗塞面积。通过分析血浆中的肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平来评估心脏损伤程度。与对照组(I/R)相比,OT 0.001、0.01 和 0.1 微克的腹腔内给药显著减少了梗塞面积、LDH 和 CK-MB 水平,并且对缺血/再灌注损伤具有双相作用。这种双相作用表现为一条 U 形曲线,其中在极低和极高剂量之间的疗效最佳。此外,在 I/R 期间,OT 治疗组和对照组之间的平均动脉压或心率没有显著差异。阿托西班(10(-6)M)阻断特定的 OT 受体,消除或减弱了 OT 预处理的作用。这项研究的结果表明,OT 对缺血/再灌注损伤具有剂量依赖性的心脏保护作用,因此对 OT 预处理的研究可能为治疗靶点的开发提供新的靶点。

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