Differential cardioprotective effects of salvianolic acid and tanshinone on acute myocardial infarction are mediated by unique signaling pathways
Differential cardioprotective effects of salvianolic acid and tanshinone on acute myocardial infarction are mediated by unique signaling pathways
复制标题
丹酚酸和丹参酮对急性心肌梗死的不同心脏保护作用是由独特的信号通路介导的
DOI：
10.1016/j.jep.2011.03.070
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Gao, Xiumei
中科院分区：
文献类型：
--
作者：
Wang, Xiaoying;Wang, Yi;Gao, Xiumei
民族药理学相关性：丹参酮（TAN）和丹参酮（SAL）分别是丹参中的主要亲水性和亲脂性化合物，在亚洲国家已被广泛应用于心血管疾病的治疗。由于很少有研究报道了不同的化合物在同一草药之间的不同分子机制，我们调查，如果单独的分子途径参与心肌保护作用的不同活性成分Danshen.Materials和方法：我们使用了一个急性心肌梗死（MI）模型，比较SAL和TAN在大鼠的心脏保护作用。分别于术后3、7、14、28天观察心肌梗死面积和超声心动图反应。结果：SAL和TAN均可通过缩小心肌梗死面积和改善心肌收缩功能延缓心肌缺血的发展。基因本体论和京都基因和基因组百科全书（KEGG）途径分析表明SAL和TAN的动力学和基因表达谱不同。SAL在缺血后的后期发挥作用，其作用可能是通过下调参与氧化应激、某些G蛋白偶联受体活性和细胞凋亡的基因介导的。另一方面，TAN在缺血损伤后相对较早地起作用，其作用至少部分是通过抑制细胞内钙、细胞粘附和补体旁路途径介导的。引人注目的是，我们发现，TAN，最近确定的选择性雌激素受体修饰剂（SERM）的成员，确实调节已知参与雌激素代谢后MI.Conclusions基因：虽然SAL和TAN都有助于丹参的心脏保护作用，有显着的机制和时间差异两者之间：TAN主要通过抑制细胞内钙和细胞粘附途径在缺血损伤后早期发挥作用，而SAL主要通过下调细胞凋亡发挥作用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Ethnopharmacological relevance: Salvianolic acid (SAL) and tanshinone (TAN) are major hydrophilic and lipophilic compounds, respectively, from one herbal medicine, Danshen, which has been widely and successfully used for treating cardiovascular diseases in Asian countries. Because few studies have reported different molecular mechanisms between the different compounds in same herb, we investigate if separate molecular pathways are involved in cardioprotective effect by different active components of Danshen.Materials and methods: We used an acute myocardial infarction (MI) model to compare the cardioprotective effects of SAL and TAN in rats. Both infarct size and echocardiographic response were evaluated at 3, 7,14 and 28 days after surgery. Genes involved in ischemic injury and in responses to SAL or TAN treatment in ischemic hearts were identified by microarray analysis and verified by quantitative real-time RT-PCR.Results: Results showed that both SAL and TAN delay the development of ischemia by decreasing infarct size and improving systolic function post MI. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated different kinetics and gene expression profiles by SAL and TAN. SAL acts in a later period after ischemia, and its effect is probably mediated by downregulation of genes involved in oxidative stress, certain G-protein coupled receptor activities and apoptosis. On the other hand, TAN acts relatively early after ischemic injury and its effect is at least in part mediated by inhibition of intracellular calcium, cell adhesion and alternative complement pathway. Strikingly, we found that TAN, a recently identified member of selective estrogen receptor modifier (SERM), indeed regulates genes known to be involved in estrogen metabolism post MI.Conclusions: Although both SAL and TAN contribute to the cardioprotective effect of Danshen, there are significant mechanistic and temporal differences between the two: TAN acts at an early stage after ischemic injury mainly by inhibition of intracellular calcium and cell adhesion pathways whereas SAL acts mainly by down-regulating apoptosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.