Cardioprotective Natural Compound Pinocembrin Attenuates Acute Ischemic Myocardial Injury via Enhancing Glycolysis.
Cardioprotective Natural Compound Pinocembrin Attenuates Acute Ischemic Myocardial Injury via Enhancing Glycolysis.
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具有心脏保护作用的天然化合物 Pinocembrin 通过增强糖酵解减轻急性缺血性心肌损伤
DOI：
10.1155/2020/4850328
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发表时间：
2020
影响因子：
--
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Zheng Y;Wan G;Yang B;Gu X;Lin J
目的 新的证据表明，松香素可保护动物心肌免受缺血性损伤。然而，尚不清楚在再灌注开始时给予它是否具有心脏保护作用。此外，介导松香素心脏保护作用的机制在很大程度上也是未知的。因此，本研究旨在探讨松柏素后处理对缺血再灌注（I/R）损伤的影响及其潜在机制。方法采用体内小鼠心肌I/R损伤模型、离体大鼠离体心脏整体I/R以及体外原代心肌细胞缺氧/复氧（H/R）损伤模型。结果我们发现松香素后处理可显着减少急性心肌缺血再灌注后的梗塞面积并改善心脏收缩功能。从机械角度来看，在原代心肌细胞中，我们发现松香素可能部分通过促进糖酵解酶 PFKFB3 的表达直接刺激心脏糖酵解来提供保护。此外，PFKFB3 抑制作用消除了松香素诱导的糖酵解和对心肌细胞的保护。更重要的是，通过心肌腺相关病毒（AAV）敲低 PFKFB3 消除了松柏素的心脏保护作用。此外，我们证明 HIF1α 是驱动松香素诱导的心肌细胞中 PFKFB3 表达的关键转录因子。结论 总之，这些结果证实松柏素的急性心脏保护作用部分是通过 HIF1α 增强 PFKFB3 介导的糖酵解来介导的，这可能为阻止心肌 I/R 损伤的进展提供新的治疗靶点。
Purpose Emerging evidence has shown that pinocembrin protects the myocardium from ischemic injury in animals. However, it is unknown whether it has cardioprotection when given at the onset of reperfusion. Also, mechanisms mediating the cardioprotective actions of pinocembrin were largely unknown. Thus, this study is aimed at investigating the effects of pinocembrin postconditioning on ischemia-reperfusion (I/R) injury and the underlying mechanisms. Methods The in vivo mouse model of myocardial I/R injury, ex vivo isolated rat heart with global I/R, and in vitro hypoxia/reoxygenation (H/R) injury model for primary cardiomyocytes were used. Results We found that pinocembrin postconditioning significantly reduced the infarct size and improved cardiac contractile function after acute myocardial I/R. Mechanically, in primary cardiomyocytes, we found that pinocembrin may confer protection in part via direct stimulation of cardiac glycolysis via promoting the expression of the glycolytic enzyme, PFKFB3. Besides, PFKFB3 inhibition abolished pinocembrin-induced glycolysis and protection in cardiomyocytes. More importantly, PFKFB3 knockdown via cardiotropic adeno-associated virus (AAV) abrogated cardioprotective effects of pinocembrin. Moreover, we demonstrated that HIF1α is a key transcription factor driving pinocembrin-induced PFKFB3 expression in cardiomyocytes. Conclusions In conclusion, these results established that the acute cardioprotective benefits of pinocembrin are mediated in part via enhancing PFKFB3-mediated glycolysis via HIF1α, which may provide a new therapeutic target to impede the progression of myocardial I/R injury.
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影响因子：
4.4
作者：
Saad, Muhammed A.;Salam, Rania M. Abdel;Attia, Amina S.
通讯作者：
Attia, Amina S.
影响因子：
6.1
作者：
Shi, Li-li;Chen, Bai-nian;Du, Guan-hua
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Du, Guan-hua
影响因子：
37.8
作者：
Malmberg, K;Norhammar, A;Rydén, L
通讯作者：
Rydén, L
影响因子：
2.6
作者：
Hunter, A. J.;Hendrikse, A. S.;Renan, M. J.
通讯作者：
Renan, M. J.
DOI：
10.1152/ajpheart.00495.2012
发表时间：
2013-08-01
影响因子：
4.8
作者：
Irvine, Jennifer C.;Cao, Nga;Ritchie, Rebecca H.
通讯作者：
Ritchie, Rebecca H.