Loss of Cardioprotection With Ischemic Preconditioning in Aging Hearts: Role of Sirtuin 1?
Loss of Cardioprotection With Ischemic Preconditioning in Aging Hearts: Role of Sirtuin 1?
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DOI：
10.1177/1074248412458723
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发表时间：
2013-01-01
影响因子：
2.6
通讯作者：
Lecour, Sandrine
中科院分区：
文献类型：
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作者：
Adam, Tasneem;Sharp, Stephanie;Lecour, Sandrine
缺血预适应(IPC)对心脏缺血/再灌注损伤(IRI)的保护作用随年龄增长而下降。脱乙酰酶蛋白sirtuin 1(Sirt 1)具有多种功能，包括长寿和对IRI的心脏保护。因此，Sirt 1可能是解释IPC保护作用的潜在候选基因。我们旨在探讨Sirt-1在IPC心脏保护作用随年龄增长而丧失的过程中的作用。分别从年轻(9周)和老年(12-18个月)的Long-Evans大鼠分离心脏，进行30分钟的全脑缺血和60分钟的再灌流。预适应刺激采用2个循环的5min缺血/再灌流，或给予Sirt1激动剂白藜芦醇(RSV，10MU/L)15min，然后在持续缺血前冲洗10min。IPC和RSV均显著促进年轻心脏的功能恢复，分别为对照组的168%(P<；.001)和对照组的65%(P<；.01)，同时使心肌梗死面积减少65%和45%，但对老年心脏的作用减弱。对年轻心脏给予选择性Sirt-1抑制剂III并不改变IPC的保护作用。在缺血/再灌注后，与年轻心脏相比，老年心脏的Sirt1脱乙酰酶活性更高(0.48+/-0.13任意单位[AU]比0.17+/-0.03AU，P<；0.01)，而IPC不改变Sirt1脱乙酰酶的活性。综上所述，尽管Sirt1脱乙酰酶活性在缺血/再灌注期间随年龄增加而增加，但我们的数据表明，在老年动物中，IPC的心脏保护作用的丧失可能与Sirt1无关。
The effectiveness of ischemic preconditioning (IPC) to protect the heart against ischemia/reperfusion injury (IRI) declines with age. The deacetylase protein sirtuin 1 (Sirt 1) confers myriad functions including longevity and cardioprotection against IRI. As such, Sirt 1 may be a potential candidate to explain the protective effect of IPC. We aim to explore the role of Sirt 1 in the loss of the cardioprotective effect of IPC with age. Isolated hearts from young (9 weeks) and older (12-18 months) Long-Evans rats were subjected to 30 minutes of global ischemia and 60 minutes of reperfusion. Preconditioning stimuli were applied with either 2 cycles of 5-minute ischemia/reperfusion or with the potent Sirt 1 agonist resveratrol (RSV, 10 mu mol/L) for 15 minutes followed by a 10-minute washout before the sustained ischemia. Both IPC and RSV significantly enhanced the functional recovery of young hearts by 168% (P < .001 vs control) and 65% (P < .01 vs control), respectively, and concomitantly reduced the infarct size by 65% and 45%, but the effect was blunted in older hearts. Administration of the selective Sirt 1 inhibitor III to young hearts did not alter the protective effect of IPC. Following ischemia/reperfusion, higher Sirt 1 deacetylase activity was detected in older hearts compared to young hearts (0.48 +/- 0.13 arbitrary units [AU] vs 0.17 +/- 0.03 AU, P < .01) and IPC did not alter Sirt 1 deacetylase activity. In conclusion, although Sirt 1 deacetylase activity is increased with age during ischemia/reperfusion, our data suggest that the loss of the cardioprotective effect of IPC in older animals is likely to be independent of Sirt 1.