Zheng Hong, Guo Hai, Hong Yi, Zheng Fen, Wang Jiang
Department of Anaesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Department of Cardiac Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Eur J Cardiothorac Surg. 2015 Sep;48(3):375-81. doi: 10.1093/ejcts/ezu494. Epub 2015 Feb 24.
The loss of effectiveness of ischaemic preconditioning in protecting old hearts from ischaemia/reperfusion damage is thought to be due to low sirtuin 1 levels in old hearts. We sought to determine whether resveratrol (RES), an activator of sirtuin 1, would restore this protection to that seen with ischaemic preconditioning in young hearts.
A Langendorff heart perfusion model was established in 80 old and 80 adult rats to test the effects of hypoxic preconditioning (HPC) and/or RES on preventing hypoxia-reperfusion (H/R) injury. The effects were further tested by comparing the effects of HPC and RES on cell survival rate and lactate dehydrogenase (LDH) in cardiomyocytes from 15 old and 15 young humans.
The HPC + RES group performed better in both adult and old groups than the corresponding H/R, HPC and RES groups, causing ∼50% in the adult and 40% in the old group restoration of left ventricular developed pressure and ∼90% in the adult and 80% in the old group restoration of dp/dtmax. HPC and RES each reduced apoptosis in both groups. The HPC + RES treatment showed an additive benefit in reducing apoptosis in the adult group but not in the old group. In H/R-treated young and old human cardiomyocytes, cell survival and LDH level were significantly improved in the RES + HPC group compared with the HPC group.
This study showed that RES lessened the ageing effect and enhanced the cardioprotective effect of HPC in older individuals.
缺血预处理对老年心脏缺血/再灌注损伤的保护作用失效被认为是由于老年心脏中沉默调节蛋白1水平较低。我们试图确定白藜芦醇（RES），一种沉默调节蛋白1的激活剂，是否能将这种保护作用恢复到年轻心脏缺血预处理时的水平。
在80只老年大鼠和80只成年大鼠中建立Langendorff心脏灌注模型，以测试缺氧预处理（HPC）和/或RES对预防缺氧-再灌注（H/R）损伤的作用。通过比较HPC和RES对15名老年人和15名年轻人心肌细胞存活率和乳酸脱氢酶（LDH）的影响，进一步测试其效果。
在成年组和老年组中，HPC + RES组的表现均优于相应的H/R、HPC和RES组，使成年组左心室舒张末压恢复约50%，老年组恢复约40%；使成年组dp/dtmax恢复约90%，老年组恢复约80%。HPC和RES均降低了两组的细胞凋亡率。HPC + RES治疗在降低成年组细胞凋亡方面显示出相加的益处，但在老年组中未显示出该效果。在H/R处理后的年轻人和老年人心肌细胞中，RES + HPC组的细胞存活率和LDH水平与HPC组相比有显著改善。
本研究表明，RES减轻了衰老效应，并增强了HPC对老年人的心脏保护作用。
