Yamazaki Katrina Go, Romero-Perez Diego, Barraza-Hidalgo Maraliz, Cruz Michelle, Rivas Maria, Cortez-Gomez Brenda, Ceballos Guillermo, Villarreal Francisco
Department of Medicine, UCSD Cardiology, 9500 Gilman Dr. 0613J, BSB 4028, La Jolla, CA 92093, USA.
Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H761-7. doi: 10.1152/ajpheart.00413.2008. Epub 2008 Jun 20.
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 approximately 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.
流行病学研究表明，富含黄酮类化合物的饮食与改善心血管预后之间存在关联。可可含有大量黄酮类化合物，尤其是黄烷醇（主要是儿茶素和表儿茶素）。黄酮类化合物具有多效性，可能在组织损伤时赋予保护作用。我们研究了表儿茶素减轻短期和长期缺血再灌注（I/R）心肌损伤的能力。通过每日经口灌胃给予雄性大鼠表儿茶素（1mg·kg⁻¹·天⁻¹）预处理（Tx），持续2天或10天。对照组给予水。通过45分钟冠状动脉闭塞诱导缺血。在Tx持续的情况下，允许再灌注至48小时或3周。我们在48小时组中测量了梗死（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。在3周组中也评估了心脏形态学。Tx 2天后，MI面积没有减少。10天后，MI面积显著减少约50%。表儿茶素组大鼠的血流动力学无显著变化。与对照组相比，表儿茶素组的组织氧化应激显著降低。表儿茶素处理后梗死区域的MMP-9活性仅略有增加。到3周时，Tx组梗死面积显著减少32%，同时血流动力学持续稳定，心室形态保持正常。总之，表儿茶素预处理在I/R损伤情况下具有心脏保护作用。其作用独立于血流动力学变化，随时间持续存在，并伴有组织损伤指标水平降低。这些结果值得评估可可黄烷醇作为限制缺血性损伤的可能治疗药物。
