Bergenin alleviates myocardial ischemia-reperfusion injury via SIRT1 signaling.
Bergenin alleviates myocardial ischemia-reperfusion injury via SIRT1 signaling.
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DOI：
10.1016/j.biopha.2022.114100
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发表时间：
2022-12
期刊：
影响因子：
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通讯作者：
Yingying Liu;Yanzhen Tan;G. Cao;Lei Shi;Yujie Song;Wenju Shan;Miao Zhang;Panpan Li;
中科院分区：
文献类型：
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作者：
Yingying Liu;Yanzhen Tan;G. Cao;Lei Shi;Yujie Song;Wenju Shan;Miao Zhang;Panpan Li;
心肌缺血再灌注（MI/R）是心血管疾病的主要危险因素。目前，减少氧化应激和细胞凋亡是改善MI/R损伤的重要治疗策略。然而，目前尚缺乏针对氧化应激和细胞凋亡的药物用于MI/R的临床治疗。岩白菜素是一种有效的抗氧化剂和抗凋亡活性对急性损伤。然而，岩白菜素抗MI/R损伤的作用和潜在机制尚不清楚。在此，我们假设岩白菜素通过SIRT 1减弱MI/R诱导的细胞凋亡和活性氧（ROS）的产生。采用小鼠心肌缺血再灌注模型，观察岩白菜素对心肌缺血再灌注损伤小鼠心功能、心肌细胞凋亡、LDH释放、MDA含量的影响，并观察岩白菜素对心肌缺血再灌注损伤小鼠H9 c2细胞凋亡及氧化应激的影响。岩白菜素能显著减少体外心肌细胞凋亡和活性氧的产生，改善体内心功能。有趣的是，岩白菜素显着降低心肌细胞凋亡伴随SIRT 1上调MI/R损伤。进一步的研究表明，抑制SIRT 1阻断岩白菜素对SI/R损伤后细胞凋亡的有益影响，通过过度的氧化应激和Bcl 2与Bax比率的抑制。这些结果表明岩白菜素通过改善心肌细胞凋亡和氧化损伤蛋白SIRT 1信号通路减轻MI/R损伤。
Myocardial ischemia-reperfusion (MI/R) is a major risk factor for cardiovascular disease. At present, reducing oxidative stress and apoptosis is a crucial therapeutic strategy for ameliorating MI/R injury. However, there is a lack of drugs targeting oxidative stress and apoptosis for the clinical therapy of MI/R. Bergenin is a reportedly effective agent with antioxidative and antiapoptotic activity against acute injury. Nevertheless, the roles and potential mechanisms of bergenin against MI/R injury remain unknown. Here, we hypothesized that bergenin attenuated MI/R-induced apoptosis and reactive oxygen species (ROS) productionviaSIRT1. Mice were subjected to MI/R and treated with bergenin, after which the cardiac function, cardiomyocyte apoptosis, LDH release, and MDA content were evaluated.In vitro, myocardial injury model of H9c2 cells was induced by simulated ischemia/reperfusion (SI/R), apoptosis and oxidative stress was decreased after treated with bergenin. Bergenin significantly reduced myocardial apoptosis and ROS generationin vitroand improved cardiac functionin vivo. Intriguingly, bergenin remarkably decreased apoptosis in cardiac tissue accompanied by SIRT1 upregulation following MI/R injury. Further studies showed that inhibiting SIRT1 blocked bergenin’s beneficial impact against apoptosis following SI/R injury through excessive oxidative stress and depression of the Bcl2 to Bax ratio. Collectively, these findings indicate that bergenin alleviates MI/R injury by ameliorating myocardial apoptosis and oxidative damageviathe SIRT1 signaling pathway.