Pharmacy of College, Shihezi University, Xinjiang, 832002, PR China; First Affiliated Hospital of the Medical College, Shihezi University, XinJiang, 832008, PR China.
First Affiliated Hospital of the Medical College, Shihezi University, XinJiang, 832008, PR China.
J Pharmacol Sci. 2019 Apr;139(4):352-360. doi: 10.1016/j.jphs.2019.02.008. Epub 2019 Mar 8.
Mitochondrial energy metabolism and oxidative stress play a crucial role in ameliorating myocardial ischemia/reperfusion injury (MIRI). Tilianin has been reported to have a significant protection for mitochondrion in MIRI. However, the underlying mechanisms remain unknown. This study investigated whether Tilianin regulates mitochondrial energy metabolism and oxidative stress in MIRI via AMPK/SIRT1/PGC-1 alpha signaling pathway. The MIRI model was established by 30 min of coronary occlusion followed by 2 h of reperfusion in rats. The results revealed that Tilianin significantly reduced myocardial infarction, improved the pathological morphology of myocardium, markedly increased the contents of ATP and NAD, decreased ADP and AMP contents and the ratio of AMP/ATP, reduced the level of ROS and MDA, enhanced SOD activity, evidently increased the levels of AMPK, SIRT1 and PGC-1 alpha mRNA, up-regulated the expressions of AMPK, pAMPK, SIRT1, PGC-1alpha, NRF1, TFAM and FOXO1 proteins. However, these effects were respectively abolished by Compound C (a specific AMPK inhibitor) and EX-527 (a specific SIRT1 inhibitor). Taken together, this study found that Tilianin could attenuate MIRI by improving mitochondrial energy metabolism and reducing oxidative stress via AMPK/SIRT1/PGC-1 alpha signaling pathway.
线粒体能量代谢和氧化应激在改善心肌缺血/再灌注损伤（MIRI）中起着至关重要的作用。据报道，三叶海棠素对 MIRI 中的线粒体具有显著的保护作用。然而，其潜在的机制仍不清楚。本研究通过 AMPK/SIRT1/PGC-1α信号通路探讨三叶海棠素是否通过调节线粒体能量代谢和氧化应激来改善 MIRI。通过在大鼠中进行 30 分钟的冠状动脉闭塞再灌注 2 小时来建立 MIRI 模型。结果表明，三叶海棠素能显著减少心肌梗死面积，改善心肌病理形态，显著增加 ATP 和 NAD 的含量，降低 ADP 和 AMP 的含量及 AMP/ATP 比值，降低 ROS 和 MDA 水平，增强 SOD 活性，明显增加 AMPK、SIRT1 和 PGC-1α mRNA 的水平，上调 AMPK、pAMPK、SIRT1、PGC-1α、NRF1、TFAM 和 FOXO1 蛋白的表达。然而，这些作用分别被化合物 C（一种特定的 AMPK 抑制剂）和 EX-527（一种特定的 SIRT1 抑制剂）所阻断。综上所述，本研究发现三叶海棠素通过激活 AMPK/SIRT1/PGC-1α 信号通路改善线粒体能量代谢和减少氧化应激来减轻 MIRI。
