Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury
Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury
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DOI：
10.1152/ajpheart.00413.2008
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发表时间：
2008-08-01
影响因子：
4.8
通讯作者：
Villarreal, Francisco
中科院分区：
文献类型：
--
作者：
Yamazaki, Katrina Go;Romero-Perez, Diego;Villarreal, Francisco
流行病学研究表明，富含类黄酮的饮食与改善心血管预后之间存在相关性。可可含有大量黄酮类化合物，特别是黄烷醇（主要是儿茶素和表儿茶素）。黄酮类化合物具有多效性，可在损伤期间对组织产生保护作用。我们研究了表儿茶素减少短期和长期缺血再灌注（I/R）心肌损伤的能力。表儿茶素（1 mg . kg（-1）。第（-1）天）预处理（Tx）通过口服管饲法每天给予雄性大鼠2或10天。对照组接受水。通过45分钟的冠状动脉闭塞诱导缺血。允许再灌注至48 h或3 wk，同时继续Tx。我们测量了48小时组的梗死（MI）面积（%）、血流动力学、髓过氧化物酶活性、组织氧化应激和基质金属蛋白酶-9（MMP-9）活性。3周组还进行了心脏形态学评价。Tx治疗2天后，MI大小未减少。10天后，MI尺寸显著减小，相似于50%。表儿茶素对大鼠血流动力学无明显影响。与对照组相比，表儿茶素组的组织氧化应激显著降低。MMP-9的活性表现出有限的增加，在梗塞区与表儿茶素。到第3周，观察到与Tx，伴随着持续的血流动力学和保存腔室形态学梗死面积的显着减少32%。总之，表儿茶素Tx在I/R损伤的情况下赋予心脏保护作用。这些影响不依赖于血液动力学的变化，随着时间的推移而持续，并伴随着组织损伤指标水平的降低。结果证明可可黄烷醇作为限制缺血性损伤的可能治疗剂的评价是合理的。
Epidemiological studies have shown a correlation between flavonoid-rich diets and improved cardiovascular prognosis. Cocoa contains large amounts of flavonoids, in particular flavanols (mostly catechins and epicatechins). Flavonoids possess pleiotropic properties that may confer protective effects to tissues during injury. We examined the ability of epicatechin to reduce short-and long-term ischemia-reperfusion (I/R) myocardial injury. Epicatechin (1 mg . kg(-1) . day(-1)) pretreatment (Tx) was administered daily via oral gavage to male rats for 2 or 10 days. Controls received water. Ischemia was induced via a 45-min coronary occlusion. Reperfusion was allowed until 48 h or 3 wk while Tx continued. We measured infarct (MI) size (%), hemodynamics, myeloperoxidase activity, tissue oxidative stress, and matrix metalloproteinase-9 (MMP-9) activity in 48-h groups. Cardiac morphometry was also evaluated in 3-wk groups. With 2 days of Tx, no reductions in MI size occurred. After 10 days, a significant similar to 50% reduction in MI size occurred. Epicatechin rats demonstrated no significant changes in hemodynamics. Tissue oxidative stress was reduced significantly in the epicatechin group vs. controls. MMP-9 activity demonstrated limited increases in the infarct region with epicatechin. By 3 wk, a significant 32% reduction in infarct size was observed with Tx, accompanied with sustained hemodynamics and preserved chamber morphometry. In conclusion, epicatechin Tx confers cardioprotection in the setting of I/R injury. The effects are independent of changes in hemodynamics, are sustained over time, and are accompanied by reduced levels of indicators of tissue injury. Results warrant the evaluation of cocoa flavanols as possible therapeutic agents to limit ischemic injury.