The saponin of red ginseng protects the cardiac myocytes against ischemic injury in vitro and in vivo
The saponin of red ginseng protects the cardiac myocytes against ischemic injury in vitro and in vivo
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DOI：
10.1016/j.phymed.2012.01.002
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发表时间：
2012-04-15
期刊：
影响因子：
7.9
通讯作者：
Tu, Peng-Fei
中科院分区：
文献类型：
--
作者：
Li, Hai-Xia;Han, Shu-Yan;Tu, Peng-Fei
人参蒸根，又称红参，在皂苷成分和含量上与其他人参制剂有所不同，因为在蒸制过程中会产生一些部分脱糖的皂苷作为人工制品。然而，红参皂苷(SRG)对心肌细胞是否具有保护作用尚不清楚。本研究旨在探讨SRG对体内外心肌缺血的影响。四甲基偶氮唑盐比色法显示，SRG可显著提高Na2S2O4缺氧损伤的心肌细胞的存活率。这种作用可被ATP敏感性钾通道阻断剂格列本脲几乎完全消除，但磷脂酰肌醇3-激酶(PI3K)抑制剂LY294002不影响SRG的心肌保护作用。流式细胞仪的Fluo-3/AM探针显示，SRG还显著降低Na2S2O4诱导的细胞内钙的增加。采用结扎冠状动脉左前降支造成的成年大鼠心肌缺血模型进行在体分析。SRG可缩小心肌梗死面积，增加缺血后2 4h的左心室发展压、左心室(+)dp/dt(Max)和左心室收缩压，降低左心室(-)dp/dt(Max)和左心室舒张末压力。此外，SRG显著降低血清中心肌肌钙蛋白I(CTnI)的水平，这表明cTnI是参与心脏收缩能力的肌钙蛋白调节复合体的一种蛋白质成分，有助于SRG介导的心脏收缩功能的恢复。总之，这项研究首次为SRG的心脏保护作用提供了证据和机制分析。SRG通过改善心脏收缩功能，部分通过减少cTnI分泌，改善心脏舒张期功能，从而显著减轻心肌缺血损伤。此外，SRG还可减轻心肌细胞内钙超载，并调节K-ATP信号通路，但不调节PI3K信号通路；总之，这些机制协同作用减少了心肌梗死面积。(C)2012年爱思唯尔股份有限公司。版权所有。
Steamed root of Panax ginseng C.A. Mayer, known as "red ginseng", differs from other ginseng preparations in terms of its saponin components and content, as some partly deglycosylated saponins are produced as artifacts during the steaming process. However, whether saponins derived from red ginseng (SRG) can have a protective effect on cardiomyocytes remains unknown. The present study aimed to explore the effect of SRG on myocardial ischemia in vitro and in vivo. MTT assays revealed that SRG pretreatment significantly increased the viability of cardiomyocytes injured by Na2S2O4 hypoxia in vitro. This effect was almost completely abolished by glibenclamide, a blocker of the ATP-sensitive potassium channel, but the cardioprotective activity of SRG was not influenced by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.SRG also significantly reduced the Na2S2O4-induced increase in intracellular calcium, as shown by Fluo-3/AM probes with flow cytometry. Adult rat heart ischemia, which was induced by ligation of the left anterior descending coronary artery, was employed for the in vivo analysis. SRG pretreatment reduced infarct size and resulted in a higher left ventricle (LV) developed pressure, LV (+)dP/dt(max) and LV systolic pressure and lower LV (-)dP/dt(max) and LV end diastolic pressure after 24h of ischemia. Moreover, SRG significantly reduced the level of cardiac Troponin I(cTnI) in the serum, which suggests that cTnI, a protein component of the troponin regulatory complex involved in cardiac contractility, contributes to the SRG-mediated recovery of cardiac systolic function. In conclusion, this study is the first to provide evidence and a mechanistic analysis of the cardioprotective effects of SRG. SRG significantly attenuated myocardial ischemic injury by improving cardiac systole function, partly by reducing cTnI secretion and improving cardiac diastolic function. Also, SRG attenuated the Ca2+ overload in cardiomyocytes and modulated the K-ATP, but not PI3K, signaling pathway; taken together, these mechanisms synergistically reduced infarct size. (C) 2012 Elsevier GmbH. All rights reserved.