Short-term caloric restriction improves ischemic tolerance independent of opening of ATP-sensitive K+ channels in both young and aged hearts
Short-term caloric restriction improves ischemic tolerance independent of opening of ATP-sensitive K+ channels in both young and aged hearts
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DOI：
10.1016/j.yjmcc.2005.03.010
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发表时间：
2005-08-01
影响因子：
5
通讯作者：
Bolli, R
中科院分区：
文献类型：
--
作者：
Shinmura, K;Tamaki, K;Bolli, R
缺血耐受性随增龄而降低，缺血预处理（IPC）的心脏保护作用在老年动物中受到损害。虽然终身热量限制（CR）深刻影响衰老引起的生理和病理生理变化，并显着增加寿命在几个物种，目前还不清楚是否短期CR影响缺血耐受性和IPC在老年心脏。将6月龄（Y）和24月龄（O）Fischer 344只雄性大鼠随机分为两组; AL大鼠自由采食，而CR大鼠饲喂AL 90%的热量摄入2周，然后饲喂65%的热量摄入2周。离体灌流心脏进行25分钟的缺血，然后再灌注30分钟，有或没有IPC。IPC可改善ALY再灌注后左室功能的恢复，但对ALO无明显影响。CR可促进CRY和CRO的左室功能恢复，但IPC的心脏保护作用与CR的作用不相加。5-羟基癸酸酯和格列本脲均不能消除CR对CRY或CRO的保护作用。在两代中，CR再灌注后心肌高能磷酸盐的恢复更好。Y组和O组心肌AMPK表达水平无差异，但在Thr（172）磷酸化的AMPK-a表达水平随CR增加而增加。总之，短期CR改善心肌缺血耐受性与Y和O的KATP通道开放无关。CR诱导的心脏保护作用与激活AMPK的增加有关。(c)2005爱思唯尔有限公司保留所有权利。
Ischemic tolerance decreases with aging and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in aged animals. Although lifelong caloric restriction (CR) profoundly affects the physiological and pathophysiological modifications induced by aging and markedly increases life span in several species, it is unclear whether short-term CR affects ischemic tolerance and IPC in aged hearts. Six-month-old (Y) and 24-month-old (O) Fischer 344 male rats were randomly divided into two groups; AL rats were fed ad libitum, whereas CR rats were fed 90% of the caloric intake of AL for 2 weeks followed by 65% of the caloric intake for 2 weeks. Isolated perfused hearts were subjected to 25 min of ischemia followed by 30 min of reperfusion with or without IPC. The recovery of LV function after reperfusion improved with IPC in ALY but not in ALO. CR improved the recovery of LV function in both CRY and CRO but the cardioprotective effect of IPC was not additive to that of CR. Neither 5-hydroxydecanoate nor glibenclamide abrogated the protective effect of CR in either CRY or CRO. The recovery of myocardial high-energy phosphates after reperfusion was better with CR in both generations. There was no difference in myocardial expression levels of AMP-activated kinase (AMPK) but AMPK-a phosphorylated at Thr(172) increased with CR in both Y and O. In conclusion, short-term CR improves myocardial ischemic tolerance independent of the opening of KATP channels in both Y and O. CR-induced cardioprotection is associated with an increase in activated AMPK. (c) 2005 Elsevier Ltd. All rights reserved.