Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, China.
Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
Biofactors. 2022 May;48(3):651-664. doi: 10.1002/biof.1820. Epub 2022 Feb 7.
This study was designed to investigate whether berbamine (BA)-induced cardioprotective effects were related to 5' adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor (Nrf2) signaling and changes in the mitochondria in myocardial ischemia/reperfusion (I/R) injury. C57/BL6 mice were exposed to BA (10 mg/kg/d), with or without administration of the AMPK specific inhibitor compound C (5 mg/kg/d) or the Nrf2 specific inhibitor ML-385 (30 mg/kg/d), and then subjected to a myocardial I/R operation. As expected, BA significantly improved post-ischemic cardiac function, reduced infarct size and apoptotic cell death, decreased oxidative stress, and improved the mitochondrial state. Furthermore, BA markedly increased AMPK activation, Nrf2 nuclear translocation, and the levels of NAD(P)H quinone dehydrogenase and heme oxygenase-1. Nevertheless, these BA-induced changes were abrogated by compound C. In addition, ML-385 also canceled the cardioprotective effects of BA but had little effect on AMPK activation. Our results demonstrate that BA alleviates myocardial I/R injury and the mitochondrial state by inhibiting apoptosis and oxidative stress via the AMPK/Nrf2 signaling pathway.
本研究旨在探讨小檗胺（BA）诱导的心脏保护作用是否与 5' 腺苷一磷酸激活蛋白激酶（AMPK）/核因子红细胞 2 相关因子（Nrf2）信号转导和心肌缺血/再灌注（I/R）损伤中的线粒体变化有关。C57/BL6 小鼠暴露于 BA（10mg/kg/d），或同时给予 AMPK 特异性抑制剂化合物 C（5mg/kg/d）或 Nrf2 特异性抑制剂 ML-385（30mg/kg/d），然后进行心肌 I/R 手术。正如预期的那样，BA 显著改善了缺血后心脏功能，减少了梗死面积和细胞凋亡，降低了氧化应激，并改善了线粒体状态。此外，BA 显著增加了 AMPK 的激活、Nrf2 的核转位以及 NAD(P)H 醌氧化还原酶和血红素加氧酶-1 的水平。然而，这些 BA 诱导的变化被化合物 C 所阻断。此外，ML-385 也取消了 BA 的心脏保护作用，但对 AMPK 的激活影响不大。我们的结果表明，BA 通过抑制凋亡和氧化应激，通过 AMPK/Nrf2 信号通路减轻心肌 I/R 损伤和线粒体状态。
