Salvianic acid A sodium protects HUVEC cells against tert-butyl hydroperoxide induced oxidative injury via mitochondria-dependent pathway
Salvianic acid A sodium protects HUVEC cells against tert-butyl hydroperoxide induced oxidative injury via mitochondria-dependent pathway
复制标题
丹酚酸 A 钠通过线粒体依赖性途径保护 HUVEC 细胞免受叔丁基过氧化氢诱导的氧化损伤
DOI：
10.1016/j.cbi.2017.10.025
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发表时间：
2018-01-05
影响因子：
5.1
通讯作者：
Zhang, Chuan
中科院分区：
文献类型：
--
作者：
Jia, Dan;Li, Tian;Zhang, Chuan
丹参素（SalvianicAcidA，Danshensu）是从丹参（Salvia miltiorrhiza，Danshen）中提取的主要水溶性成分，在我国临床上广泛用于治疗心血管疾病。本研究旨在探讨丹参素A钠（SAAS）对叔丁基过氧化氢（t-BHP）诱导的人脐静脉内皮细胞（HUVEC）氧化损伤的保护作用及其分子机制。在抗氧化活性评估模型中，SAAS预处理显著改善t-BHP诱导的细胞生长抑制和凋亡。建立了基于超高效液相色谱/四极杆飞行时间质谱（UPLC-QTOF-MS）的HUVEC细胞代谢分析方法，研究t-BHP和SAAS对HUVEC细胞代谢的影响。结果表明，t-BHP损伤上调了13种主要参与色氨酸代谢和苯丙氨酸代谢的代谢产物，这些代谢产物与线粒体功能和氧化应激高度相关，50 μ M SAAS预处理可有效逆转这些代谢变化。进一步的生物医学研究表明，SAAS预处理可通过JAK 2/STAT 3和PI 3 K/Akt/GSK-3 β信号通路抑制t-BHP诱导的乳酸脱氢酶（LDH）、细胞内活性氧（ROS）、丙二醛（MDA）和线粒体膜电位（MMP）的升高，以及线粒体抗氧化关键酶的降低。以上结果提示，SAAS可能通过线粒体抗氧化防御系统保护HUVEC细胞免受t-BHP诱导的氧化损伤。
Salvianic acid A (Danshensu) is a major water-soluble component extracted from Salvia miltiorrhiza (Danshen), which has been widely used in clinic in China for treatment of cardiovascular diseases (CVDs). This study aimed to investigate the protective effects of salvianic acid A sodium (SAAS) against tert-butyl hydroperoxide (t-BHP) induced human umbilical vein endothelial cell (HUVEC) oxidative injury and the underlying molecular mechanisms. In the antioxidant activity-assessing model, SAAS pretreatment significantly ameliorated the cell growth inhibition and apoptosis induced by t-BHP. An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) based-metabolic profiling was developed to investigate the metabolic changes of HUVEC cells in response to t-BHP and SAAS. The results revealed that t-BHP injury upregulated 13 metabolites mainly involved in tryptophan metabolism and phenylalanine metabolism which were highly correlated with mitochondrial function and oxidative stress, and 50 mu M SAAS pretreatment effectively reversed these metabolic changes. Further biomedical research indicated that SAAS pretreatment reduced the t-BHP induced increase of lactate dehydrogenase (LDH), intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and mitochondrial membrane potential (MMP), and the decrease of key antioxidant enzymes through mitochondria antioxidative pathways via JAK2/STAT3 and PI3K/Akt/GSK-3 beta signalings. Taken together, our results suggested that SAAS may protect HUVEC cells against t-BHP induced oxidative injury via mitochondrial antioxidative defense system.