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首页> 外文期刊>International journal of molecular medicine >Synergistic cardioprotective effects of Danshensu and hydroxysafflor yellow A against myocardial ischemia-reperfusion injury are mediated through the Akt/Nrf2/HO-1 pathway
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Synergistic cardioprotective effects of Danshensu and hydroxysafflor yellow A against myocardial ischemia-reperfusion injury are mediated through the Akt/Nrf2/HO-1 pathway

机译：丹参素和羟基红花黄色素A对心肌缺血再灌注损伤的协同心脏保护作用通过Akt / Nrf2 / HO-1途径介导

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摘要

In clinical practice, the traditional Chinese medicinal herbs, Radix Salvia Miltiorrhiza and Carthamus tinctorius L., are usually prescribed in combination due to their significant cardioprotective effects. However, the mechanisms responsible for these combined effects remain unknown. Thus, in this study, we investigated the mechanisms responsible for the combined effects of Danshensu (DSS) and hydroxysafflor yellow A (HSYA) by establishing a rat model of myocardial ischemia/reperfusion (MI/R), as well as a model of hypoxia/reoxygenation (H/R) using H9c2 cells. The combination index (CI) was calculated using the median-effect method. DSS and HSYA in combination led to a CI value of <1 as regards infarct size in vivo and cell viability in vitro. The rats with MI/R injury that were treated with DSS and/or HSYA were found to have significantly lower levels of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) and malondialdehyde (MDA), and a lower expressoin of 8-hydroxydeoxyguanosine (8-OHdG), and markedly enhanced superoxide dismutase (SOD) activity. Our in vitro experiments revealed that the cells treated with DSS and/or HSYA had a reduced lactate dehydrogenase (LDH) activity and a decreased percentage of cell apoptosis (increased Bcl-2/Bax ratio, decreased expression of cleaved caspase-3). DSS and HSYA increased the expression of heme oxygenase-1 (HO-1), the phosphorylation of Akt and the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the Akt inhibitor, LY294002, partially hampered the expression of Nrf2 and HO-1. The HO-1 inhibitor, zinc protoporphyrin IX (ZnPP-IX), did not decrease the expression of p-Akt and Nrf2, although it abolished the anti-apoptotic and antioxidant effects of DSS and HSYA. The findings of our study thus demonstrate that DSS and HSYA confer synergistic cardioprotective effects through the Akt/Nrf2/HO-1 signaling pathway, to certain extent, by enhancing the antioxidant defense system and exerting anti-apoptotic effects.
机译：在临床实践中，由于其显着的心脏保护作用，通常将传统的中药丹参和红花药合用。但是，导致这些综合作用的机制仍然未知。因此，在这项研究中，我们通过建立大鼠心肌缺血/再灌注模型（MI / R）和缺氧模型，研究了丹参素（DSS）和羟基红花黄A（HSYA）联合作用的机制。 H9c2细胞进行/复氧（H / R）。组合指数（CI）使用中值效应方法计算。就体内的梗塞面积和体外细胞活力而言，DSS和HSYA的组合导致CI值<1。发现用DSS和/或HSYA治疗的MI / R损伤大鼠的肌酸激酶-MB（CK-MB）和心肌肌钙蛋白I（cTnI）和丙二醛（MDA）的水平显着降低，并且表达蛋白水平较低的8-羟基脱氧鸟苷（8-OHdG），并显着增强了超氧化物歧化酶（SOD）的活性。我们的体外实验表明，用DSS和/或HSYA处理的细胞具有降低的乳酸脱氢酶（LDH）活性和降低的细胞凋亡百分比（Bcl-2 / Bax比增加，裂解的caspase-3表达降低）。 DSS和HSYA增加了血红素加氧酶1（HO-1）的表达，Akt的磷酸化和核因子类红细胞2相关因子2（Nrf2）的易位。此外，Akt抑制剂LY294002部分阻碍了Nrf2和HO-1的表达。 HO-1抑制剂，原卟啉锌IX（ZnPP-IX），虽然消除了DSS和HSYA的抗凋亡和抗氧化作用，但并未降低p-Akt和Nrf2的表达。因此，我们的研究结果表明，DSS和HSYA通过增强抗氧化防御系统和发挥抗凋亡作用，在一定程度上通过Akt / Nrf2 / HO-1信号通路赋予了协同的心脏保护作用。

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