Honokiol Ameliorates Myocardial Ischemia/Reperfusion Injury in Type 1 Diabetic Rats by Reducing Oxidative Stress and Apoptosis through Activating the SIRT1-Nrf2 Signaling Pathway.
Honokiol Ameliorates Myocardial Ischemia/Reperfusion Injury in Type 1 Diabetic Rats by Reducing Oxidative Stress and Apoptosis through Activating the SIRT1-Nrf2 Signaling Pathway.
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和厚朴酚通过激活 SIRT1-Nrf2 信号通路减少氧化应激和细胞凋亡，从而改善 1 型糖尿病大鼠的心肌缺血/再灌注损伤
DOI：
10.1155/2018/3159801
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发表时间：
2018
影响因子：
--
通讯作者：
Yu S
中科院分区：
文献类型：
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作者：
Zhang B;Zhai M;Li B;Liu Z;Li K;Jiang L;Zhang M;Yi W;Yang J;Yi D;Liang H;Jin Z;Duan W;Yu S
减少氧化应激是改善糖尿病心肌缺血/再灌注（MI/R）损伤的重要治疗策略。本木酚（HKL）具有很强的抗氧化活性，是一种有效的心脏保护剂。然而，其在1型糖尿病（T1D）中抗MI/R损伤的作用和潜在机制尚不清楚。由于SIRT1和Nrf2是心肌梗死/R损伤的糖尿病患者的关键调节因子，我们假设HKL通过SIRT1-Nrf2信号通路改善糖尿病心肌梗死/R损伤。将链脲佐菌素诱导的T1D大鼠和高糖处理的H9c2细胞暴露于HKL，同时给予或不给予SIRT1抑制剂EX527、SIRT1 siRNA或Nrf2 siRNA，然后进行I/R操作。我们发现HKL能显著改善缺血后心功能，减少梗死面积，减少心肌凋亡，减少活性氧生成。有趣的是，HKL显著激活SIRT1信号，增强Nrf2核易位，增加抗氧化信号，减少凋亡信号。然而，这些作用在很大程度上被EX527或SIRT1 siRNA所消除。此外，我们的细胞实验表明，Nrf2 siRNA减弱了HKL的细胞保护作用，但不影响SIRT1的表达和活性。总之，这些新发现表明，HKL通过SIRT1-Nrf2信号通路改善心肌氧化损伤和细胞凋亡，从而减轻T1D的MI/R损伤。
Reducing oxidative stress is a crucial therapeutic strategy for ameliorating diabetic myocardial ischemia/reperfusion (MI/R) injury. Honokiol (HKL) acts as an effective cardioprotective agent for its strong antioxidative activity. However, its roles and underlying mechanisms against MI/R injury in type 1 diabetes (T1D) remain unknown. Since SIRT1 and Nrf2 are pivotal regulators in diabetes mellitus patients suffering from MI/R injury, we hypothesized that HKL ameliorates diabetic MI/R injury via the SIRT1-Nrf2 signaling pathway. Streptozotocin-induced T1D rats and high-glucose-treated H9c2 cells were exposed to HKL, with or without administration of the SIRT1 inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA, and then subjected to I/R operation. We found that HKL markedly improved the postischemic cardiac function, decreased the infarct size, reduced the myocardial apoptosis, and diminished the reactive oxygen species generation. Intriguingly, HKL remarkably activated SIRT1 signaling, enhanced Nrf2 nuclear translocation, increased antioxidative signaling, and decreased apoptotic signaling. However, these effects were largely abolished by EX527 or SIRT1 siRNA. Additionally, our cellular experiments showed that Nrf2 siRNA blunted the cytoprotective effects of HKL, without affecting SIRT1 expression and activity. Collectively, these novel findings indicate that HKL abates MI/R injury in T1D by ameliorating myocardial oxidative damage and apoptosis via the SIRT1-Nrf2 signaling pathway.