Extracts from Astragalus membranaceus limit myocardial cell death and improve cardiac function in a rat model of myocardial ischemia
Extracts from Astragalus membranaceus limit myocardial cell death and improve cardiac function in a rat model of myocardial ischemia
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DOI：
10.1016/j.jep.2013.07.036
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发表时间：
2013-10-07
影响因子：
5.4
通讯作者：
Tu, Pengfei
中科院分区：
文献类型：
--
作者：
Ma, Xu;Zhang, Ke;Tu, Pengfei
民族药理学相关性：黄芪的根被称为“黄芪”，是预防和治疗心肌缺血性疾病最广泛使用的中草药之一。然而，控制其治疗效果的机制在很大程度上是未知的。研究目的：研究黄芪根提取物（EAM）对心肌缺血的保护作用，并探讨其在体内外ros介导的信号级联反应中的作用机制。材料与方法：采用高效液相色谱法对EAM中皂苷进行分析。在体内和体外对EAM的心脏保护作用及其机制进行了试验。在体内，采用冠状动脉左前降支闭塞法建立大鼠持续性心肌缺血模型。在体外，用直接自由基供体H2O2模拟心肌细胞氧化应激模型。结果：在体内，经EAM预处理后，心肌梗死面积增大，血清乳酸脱氢酶（LDH）、肌酸激酶同种异构体MB （CK-MB）、心肌肌钙蛋白（cTnI）水平升高，均明显降低。此外，通过+/- dP/dt、左室发育压（LVDP）和左室舒张末期压（LVEDP）评估的心功能显著改善。氧化应激生物标志物丙二醛（MDA）被降低，抗氧化酶超氧化物歧化酶（SOD）被诱导。在体外，EAM可以阻断h2o2引发的心肌细胞死亡和细胞质Ca2+超载。此外，K-ATP、通道阻滞剂（5-HD、格列本脲）阻断了EAM对H2O2损伤心肌细胞的抗凋亡保护作用。结论：EAM对心脏的保护作用表现为对组织结构的保护作用和对缺血损伤血清标志物的降低作用。eam介导的保护作用的机制可能包括改善心功能、通过减少MDA、维持SOD和减少自由基诱导的心肌细胞损伤来减轻氧化损伤。此外，EAM通过阻止Ca2+的内流来阻止细胞死亡和打开线粒体K-ATP通道来减少细胞凋亡，从而提高心肌细胞的活力。2013爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: The root of Astragalus membranaceus, known as "huang-qi", is one of the most widely used Chinese herbal medicines for the prevention and treatment of myocardial ischemic diseases. However, the mechanisms governing its therapeutic effects are largely unknown.Aims of the study: The aims of the present study were to investigate the cardioprotective effect of the root extract of Astragalu membranaceus (EAM) in myocardial ischemia and to explore its underlying mechanisms in ROS-mediated signaling cascade in vivo and in vitro.Materials and methods: The saponins in EAM were analyzed using HPLC. The tests for the cardioprotective effects of EAM and its mechanisms were performed in vivo and in vitro. In vivo, the rat model of persistent myocardial ischemia was produced by occlusion of the left anterior descending (LAD) coronary artery. In vitro, the cardiomyocyte model of oxidative stress was mimicked by the direct free radical donor, H2O2.Results: In vivo, the Increased myocardial infarct size and the increased serum levels of lactate dehydrogenase (LDH), creatine kinase isoform MB (CK-MB), and cardiac troponin (cTnI) were significantly decreased by pre-treatment with EAM. Moreover, cardiac function, as assessed by +/- dP/dt, left ventricular developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP), was dramatically improved. An oxidative stress biomarker, malondialdehyde (MDA), was reduced, and the antioxidant enzyme superoxide dismutase (SOD) was induced. In vitro, H2O2-triggered myocardial cell death and cytoplasm Ca2+ overload were blocked by treatment with EAM. Furthermore, the K-ATP, channel blocker (5-HD, glibenclamide) blocked the anti-apoptotic protective effect of EAM on cardiomyocytes injured by H2O2.Conclusions: The cardioprotection of EAM was manifested as a protection of tissue structure and as a decrease in serum markers of ischemic injury. The mechanisms underlying the EAM-mediated protective effects may involve improving cardiac function, attenuating the oxidative injury via a decrease in MDA, a maintenance in SOD, and a reduction in free radical-induced myocardial cell injury. Additionally, EAM enhanced the myocardial cell viability via arresting the influx of Ca2+ to block cell death and opening mitochondrial K-ATP, channels to reduce cell apoptosis. (C) 2013 Elsevier Ireland Ltd. All rights reserved.