Jujuboside A attenuates norepinephrine‐induced apoptosis of H9c2 cardiomyocytes by modulating MAPK and AKT signaling pathways
Jujuboside A attenuates norepinephrine‐induced apoptosis of H9c2 cardiomyocytes by modulating MAPK and AKT signaling pathways
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Jujuboside A 通过调节 MAPK 和 AKT 信号通路减弱去甲肾上腺素诱导的 H9c2 心肌细胞凋亡
DOI：
10.3892/mmr.2017.7938
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发表时间：
2018
影响因子：
3.4
通讯作者：
Xia Zhaofei
中科院分区：
文献类型：
--
作者：
Wan Changrong;Han D;an;Xu Jianqin;Yin Peng;Xu Xiaolong;Chen Mei;Liu Fenghua;Xia Zhaofei
心肌细胞凋亡与心力衰竭的发病机制密切相关。酸枣仁皂苷A（JUA）是从酸枣仁中分离得到的一种皂苷。在传统中医学中，认为JUA具有多种生物学作用，包括抗焦虑，抗氧化和抗炎活性。本研究旨在观察杜仲酸对去甲肾上腺素（NE）诱导的H9 c2细胞凋亡的影响，并探讨其作用机制。用JUA预处理大鼠H9 c2心肌细胞，然后暴露于NE作为心肌细胞凋亡的体外模型。细胞活力测定、扫描电镜、透射电镜、流式细胞术、吖啶橙子/溴化乙锭染色、逆转录-定量聚合酶链反应和蛋白质印迹法均显示NE诱导H9 c2细胞凋亡。结果表明NE可抑制H9 c2细胞活力，增强细胞损伤和凋亡。相反，用JUA预处理能够逆转NE诱导的细胞活力下降和细胞凋亡增加。此外，JUA抑制B细胞淋巴瘤2（Bcl-2）相关的X蛋白/Bcl-2比值的上调，并抑制NE暴露后裂解的caspase-3和裂解的caspase-9蛋白表达水平的增加。然而，在暴露于NE或JUA预处理后，裂解的caspase-12和裂解的caspase-8的蛋白表达水平没有显著改变。此外，在JUA预处理的细胞中，磷酸化（p）-p38和p-c-Jun N-末端激酶的蛋白表达水平与NE处理的细胞相比下调。此外，JUA调节NE处理的细胞中细胞外信号调节激酶（ERK）的活化，并显著增加p-AKT的表达水平。综上所述，这些数据表明，JUA可能通过调节丝裂原活化蛋白激酶和AKT信号通路来保护NE诱导的心肌细胞凋亡。因此，JUA可能被认为是治疗心脏病的潜在治疗策略。
Cardiomyocyte apoptosis is closely associated with the pathogenesis of heart failure. Jujuboside A (JUA) is a type of saponin isolated from the seeds of Zizyphus jujuba. In traditional Chinese medicine, it is believed that JUA possesses multiple biological effects, including antianxiety, antioxidant and anti‐inflammatory activities. The present study aimed to evaluate the effects of JUA on norepinephrine (NE)-induced apoptosis of H9c2 cells and to investigate its underlying mechanisms. Rat H9c2 cardiomyocytes were pretreated with JUA and were then exposed to NE as an in vitro model of myocardial apoptosis. A cell viability assay, scanning electron microscopy, transmission electron microscopy, flow cytometry assay, acridine orange/ethidium bromide staining, reverse tran- scription-quantitative polymerase chain reaction and western blotting, all revealed that NE induced H9c2 cell apoptosis. The results demonstrated that NE inhibited cell viability, and enhanced cell damage and apoptosis of H9c2 cells. Conversely, pretreatment with JUA was able to reverse NE-induced decreased cell viability and increased apoptosis. Furthermore,JUA suppressed upregulation of the B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 ratio, and inhibited the increased protein expression levels of cleaved caspase-3 and cleaved caspase-9 following NE exposure. However, the protein expression levels of cleaved caspase-12 and cleaved caspase‐8 were not significantly altered following exposure to NE or JUA pretreatment. In addition, in JUA-pretreated cells, the protein expression levels of phosphorylated (p)-p38 and p-c-Jun N-terminal kinase were downregulated compared with in NE-treated cells. Furthermore, JUA regulated the activation of extracellular signal-regulated kinase (ERK) in NE‐treated cells and significantly increased the expression levels of p-AKT. Taken together, these data suggested that JUA may protect against NE-induced apoptosis of cardiomyocytes via modulation of the mitogen-activated protein kinase and AKT signaling pathways. Therefore, JUA may be considered a potential therapeutic strategy for the treatment of heart disease.