Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia-Reperfusion Injury by Modulating Energy Metabolism Pathways.

Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia-Reperfusion Injury by Modulating Energy Metabolism Pathways.
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DOI:
10.3389/fphys.2018.00078
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发表时间:
2018
影响因子:
4
通讯作者:
Han JY
Han JY
中科院分区:
医学2区
文献类型:
--
作者:
Li L;Pan CS;Yan L;Cui YC;Liu YY;Mu HN;He K;Hu BH;Chang X;Sun K;Fan JY;Huang L;Han JY

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人参皂苷Rg1(Rg1)作为人参的主要成分,对心脏健康的作用已得到越来越多的认识,但其作用机制尚不完全清楚。在H9c2心肌细胞的体外研究表明,Rg1具有增加细胞内ATP含量的潜力。因此,我们推测Rg1对心肌缺血再灌注损伤的保护作用与能量代谢调节有关。本研究旨在验证这一猜测。雄性SD大鼠结扎左冠状动脉前降支30min,再灌流90min。结扎前30min连续静脉注射Rg1(5 mg/kg/h),直至再灌流结束。I/R期间监测心肌血流量和心功能,观察再灌流90min后心肌梗死面积、结构和细胞凋亡、能量代谢及RhoA信号通路变化。用表面等离子体共振(SPR)检测Rg1与RhoA的结合。Rg1可预防心肌I/R损伤,包括心肌梗死和细胞凋亡,减少心肌血流量(MBF)和心功能,改变心肌结构。Rg1能与RhoA结合,下调RhoA信号通路的活性,恢复I/R后心肌组织中ATP的生成。提示Rg1对I/R所致心肌损伤具有保护作用,其机制可能与通过与RhoA结合来抑制心肌细胞凋亡和调节能量代谢有关。
As a major ingredient of Radix ginseng, ginsenoside Rg1 (Rg1) has been increasingly recognized to benefit the heart condition, however, the rationale behind the role is not fully understood. In vitro study in H9c2 cardiomyocytes has shown the potential of Rg1 to increase ATP content in the cells. We thus speculated that the protective effect of Rg1 on heart ischemia and reperfusion (I/R) injury implicates energy metabolism regulation. The present study was designed to verify this speculation. Male Sprague-Dawley rats were subjected to 30 min of occlusion of left coronary anterior descending artery followed by reperfusion for 90 min. Rg1 (5 mg/kg/h) was continuously administrated intravenously 30 min before occlusion until the end of reperfusion. Myocradial blood flow and heart function were monitored over the period of I/R. Myocardial infarct size, structure and apoptosis, energy metabolism, and change in RhoA signaling pathway were evaluated 90 min after reperfusion. Binding of Rg1 to RhoA was assessed using Surface Plasmon Resonance (SPR). Rg1 prevented I/R-elicited insults in myocardium, including myocardial infarction and apoptosis, decreased myocardial blood flow (MBF) and heart function, and alteration in myocardium structure. Rg1 restored the production of ATP in myocardium after I/R. Rg1 was able to bind to RhoA and down-regulate the activity of RhoA signaling pathway. These results indicated that Rg1 had protective potential against I/R-induced myocardial injury, which may be related to inhibiting myocardial apoptosis and modulating energy metabolism through binding to RhoA.
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