Atractyloside and 5-hydroxydecanoate block the protective effect of puerarin in isolated rat heart
Atractyloside and 5-hydroxydecanoate block the protective effect of puerarin in isolated rat heart
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DOI：
10.1016/j.lfs.2005.12.040
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发表时间：
2006-06-13
期刊：
影响因子：
6.1
通讯作者：
Xia, Qiang
中科院分区：
文献类型：
--
作者：
Gao, Qin;Pan, Hong-Yang;Xia, Qiang
本研究的目的是确定临床上有效的心脏保护作用所赋予的葛根素（Pue）对缺血和再灌注介导的线粒体跨膜孔和/或通道。将从雄性Sprague-Dawley大鼠分离的心脏在Langendorff装置上灌注，并进行30分钟的全脑缺血，随后进行120分钟的再灌注。通过在550 nm处的吸光度测量提供心肌存活指数的甲瓒的产生，并测定冠状动脉流出物中的乳酸脱氢酶（LDH）水平。在该模型中，Pue（0.0024-2.4 mmol/l）具有剂量依赖性负性肌力作用。缺血前用0.24 mmol/l Pue预处理5 min，可增加心肌甲含量，减少LDH释放，改善再灌注时左室舒张末压和心率-血压乘积的恢复。在再灌注的前20分钟给予线粒体通透性转换孔开放剂-在线粒体分离的心脏预处理0.24 mmol/L Pue 5分钟，观察到一个显着的抑制钙诱导的肿胀，这种抑制减弱5-羟基癸酸。在离体心室肌细胞中，Pue预处理可防止缺血诱导的细胞死亡和线粒体膜去极化，而人参皂苷和5-羟基癸酸酯可减弱Pue的作用。提示葛根素通过抑制线粒体通透性转换孔开放和激活线粒体ATP敏感性钾通道对心肌缺血再灌注损伤具有保护作用。(c)2006年爱思唯尔公司All rights reserved.
The aim of the present study was to determine whether the clinically effective cardioprotection conferred by puerarin (Pue) against ischemia and reperfusion is mediated by mitochondrial transmembrane pores and/or channels. Hearts isolated from male Sprague-Dawley rats were perfused on a Langendorff apparatus and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The production of formazan, which provides an index of myocardial viability, was measured by absorbance at 550 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was determined. In this model, Pue (0.0024-2.4 mmol/l) had a dose-dependent, negatively inotropic effect. Pretreatment with Pue at 0.24 mmol/l for 5 min before ischemia increased myocardial formazan content, reduced LDH release, improved recovery of left ventricular end-diastolic pressure and rate-pressure product (left ventricular developed pressure multiplied by heart rate) during reperfusion. Administration of atractyloside (20 mu mol/l), an opener of the mitochondrial permeability transition pore, for the first 20 min of reperfusion, and 5-hydroxydecanoate (100 mu mol/l), the mitochondrial-specific ATP-sensitive potassium channel blocker, for 20 min before ischemia, attenuated the protective effects of Pue. In mitochondria isolated from hearts pretreated with 0.24 mmol/l Pue for 5 min, a significant inhibition of Ca2+-induced swelling was observed, and this inhibition was attenuated by 5-hydroxydecanoate. In isolated ventricular myocytes, pretreatment with Pue prevented ischemia-induced cell death and depolarization of the mitochondrial membrane, and atractyloside and 5-hydroxydecanoate attenuated the effects of Pue. These findings indicate that puerarin protects the myocardium against ischemia and reperfusion injury via inhibiting mitochondrial permeability transition pore opening and activating the mitochondrial ATP-sensitive potassium channel. (c) 2006 Elsevier Inc. All rights reserved.