Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation
Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation
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DOI：
10.1159/000492257
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Shi, Dazhuo
中科院分区：
文献类型：
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作者：
Mao, Huimin;Tao, Tianqi;Shi, Dazhuo
背景/目的：Zedoarondiol是一种倍半萜内酯类化合物，在我们之前的研究中显示出对血管平滑肌细胞的抗增殖活性。然而，它是否对氧化低密度脂蛋白（ox-LDL）诱导的内皮细胞损伤有有益作用尚不清楚。本研究旨在探讨泽多环二醇对ox- ldl诱导的内皮细胞损伤的保护作用，并探讨其机制。方法：采用细胞计数试剂盒-8 （CCK-8）法和乳酸脱氢酶（LDH）活性法评价莪术酮对ox- ldl诱导的人脐静脉内皮细胞（HUVECs）损伤的保护作用。氧化应激以丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性测定。采用双乙酸二氯双氢荧光素（DCFH-DA）染色法测定活性氧（ROS）水平。收集培养上清进行白细胞介素-1 β (IL-1 β)、肿瘤坏死因子- α (tnf - α)和单核细胞趋化蛋白-1 （MCP-1）的酶联免疫吸附试验（ELISA）。免疫荧光染色观察nf - e2相关因子2 （Nrf2）易位。Western blotting检测IL-1 β、tnf - α、MCP-1、kelch样ECH相关蛋白1 （Keap1）、血红素加氧酶1 （HO-1）、NAD(P)H：醌氧化还原酶1 （NQO1）、Nrf2的表达。结果：Zedoarondiol减轻ox-LDL诱导的HUVECs损伤，上调SOD活性，抑制MDA和ROS的形成，抑制IL-1 β、tnf - α、MCP-1的分泌和蛋白表达。Zedoarondiol诱导细胞核Nrf2从细胞质转位到细胞核，并上调细胞核中HO-1、NQO1和Nrf2的表达。全反式维甲酸（ATRA），一种Nrf2抑制剂，可消除zedoarondiol介导的抗氧化作用。结论：莪术酮通过Nrf2/HO-1通路抑制氧化应激和炎症，减轻ox- ldl诱导的内皮细胞损伤，提示莪术酮可能具有预防和治疗动脉粥样硬化的作用。(c) 2018年作者：s . Karger AG， Basel出版
Background/Aims: Zedoarondiol, a sesquiterpene lactone compound, showed an anti-proliferative activity on vascular smooth muscle cells in our previous study. However, whether it has a beneficial effect on endothelial cells injury induced by oxidized low-density lipoprotein (ox-LDL) remains unclear. This study was designed to investigate the protective effect of zedoarondiol on ox-LDL-induced injury of endothelial cells and explored its underlying mechanism. Methods: The protective effect of zedoarondiol on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury were evaluated by Cell Counting Kit-8 (CCK-8) assay and released lactic dehydrogenase (LDH) activity assay. Oxidative stress was determined by malonedialdehyde (MDA) content and superoxide dismutase (SOD) activity. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The culture supernatant was collected for enzyme linked immune-sorbent assays (ELISA) of interleukine-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1). Immunofluorescence staining was used to observe NF-E2-related factor 2 (Nrf2) translocation. Western blotting was performed to determine the expression of IL-1 beta, TNF-alpha, MCP-1, Kelch-like ECH associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and Nrf2. Results: Zedoarondiol attenuated HUVECs injury, up-regulated SOD activity, suppressed formation of MDA and ROS, and secretion and protein expression of IL-1 beta, TNF-alpha, and MCP-1 in injured HUVECs induced by ox-LDL. Zedoarondiol induced nuclear Nrf2 translocation from cytoplasm into nucleus and up-regulated expression of HO-1, NQO1, and Nrf2 in nucleus. All-trans-retinoic acid (ATRA), an inhibitor of Nrf2, abolished zedoarondiol-mediated anti-oxidative effect. Conclusion: Zedoarondiol attenuates ox-LDL-induced endothelial cells injury by inhibiting oxidative stress and inflammation via Nrf2/HO-1 pathway, suggesting that zedoarondiol might be meaningful on prevention and treatment of atherosclerosis. (c) 2018 The Author(s) Published by S. Karger AG, Basel