Department of Vascular Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Institute of Life Sciences, Chongqing Medical University, Chongqing 400010, China.
Oxid Med Cell Longev. 2021 Nov 9;2021:5577019. doi: 10.1155/2021/5577019. eCollection 2021.
Myocardial ischemia-reperfusion injury (MIRI) is a phenomenon that reperfusion leads to irreversible damage to the myocardium and increases mortality in acute myocardial infarction (AMI) patients. There is no effective drug to treat MIRI. Tubeimoside I (TBM) is a triterpenoid saponin purified from Chinese traditional medicine tubeimu. In this study, 4 mg/kg TBM was given to mice intraperitoneally at 15 min after ischemia. And TBM treatment improved postischemic cardiac function, decreased infarct size, diminished lactate dehydrogenase release, ameliorated oxidative stress, and reduced apoptotic index. Notably, ischemia-reperfusion induced a significant decrease in cardiac SIRT3 expression and activity, while TBM treatment upregulated SIRT3's expression and activity. However, the cardioprotective effects of TBM were largely abolished by a SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). This suggests that SIRT3 plays an essential role in TBM's cardioprotective effects. , TBM also protected H9c2 cells against simulated ischemia/reperfusion (SIR) injury by attenuating oxidative stress and apoptosis, and siSIRT3 diminished its protective effects. Taken together, our results demonstrate for the first time that TBM protects against MIRI through SIRT3-dependent regulation of oxidative stress and apoptosis. TBM might be a potential drug candidate for MIRI treatment.
心肌缺血再灌注损伤（MIRI）是再灌注导致心肌不可逆损伤并增加急性心肌梗死（AMI）患者死亡率的现象。目前尚无治疗 MIRI 的有效药物。 苦碟子甲素（TBM）是从中药苦碟子中提取的一种三萜皂苷。本研究在缺血后 15 分钟通过腹腔内给予小鼠 4mg/kg TBM。TBM 治疗改善了缺血后的心脏功能，减少了梗死面积，降低了乳酸脱氢酶的释放，改善了氧化应激，降低了细胞凋亡指数。值得注意的是，缺血再灌注导致心脏 SIRT3 表达和活性显著降低，而 TBM 治疗上调了 SIRT3 的表达和活性。然而，SIRT3 抑制剂 3-(1H-1,2,3-三唑-4-基)吡啶（3-TYP）大大消除了 TBM 的心脏保护作用。这表明 SIRT3 在 TBM 的心脏保护作用中起关键作用。此外，TBM 通过减轻氧化应激和细胞凋亡来保护 H9c2 细胞免受模拟缺血/再灌注（SIR）损伤，而 siSIRT3 则减弱了其保护作用。综上所述，我们的研究结果首次表明，TBM 通过 SIRT3 依赖性调节氧化应激和细胞凋亡来保护 MIRI。TBM 可能是治疗 MIRI 的潜在药物候选物。
