Salidroside protects cardiomyocyte against hypoxia-induced death: A HIF-1α-activated and VEGF-mediated pathway
Salidroside protects cardiomyocyte against hypoxia-induced death: A HIF-1α-activated and VEGF-mediated pathway
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DOI：
10.1016/j.ejphar.2009.01.046
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发表时间：
2009-04-01
影响因子：
5
通讯作者：
Chen, Jianzong
中科院分区：
文献类型：
--
作者：
Zhang, Jinping;Liu, Anheng;Chen, Jianzong
心肌细胞的死亡（坏死和凋亡）在心脏疾病的发展中起着至关重要的作用。红景天苷是从红景天中分离得到的一种苯丙素苷，在体内具有心脏保护作用。然而，红景天苷是否对心肌细胞死亡有保护作用还知之甚少。本研究旨在探讨红景天苷对缺氧诱导的心肌细胞死亡的保护作用及其机制。用红景天甙预处理心肌细胞24 h后，观察缺氧6 h后心肌细胞的存活、坏死、凋亡及HIF-1 α和VEGF的表达。红景天苷预处理可明显减轻缺氧引起的细胞活力下降、细胞坏死和凋亡，且呈剂量依赖性。机制上，红景天苷预处理上调HIF-1 α蛋白表达并诱导其易位。此外，VEGF的水平，HIF的下游目标，显着增加与HIF-1 α的水平后，红景天苷预处理。然而，HIF-1 α抑制剂2-ME 2减弱了红景天苷的保护作用，并阻断了HIF-1 α和VEGF的增加。这些数据表明红景天苷通过增加HIF-1 α表达和随后上调VEGF水平对缺氧诱导的心肌细胞坏死和凋亡具有保护作用。皇冠版权所有（C）2009年出版的爱思唯尔B. V.保留所有权利。
Cardiomyocyte death (necrosis and apoptosis) plays a critical role in the progress of heart diseases. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L, has shown cardioprotective effects in vivo. However, whether salidroside has a protective effect against cardiomyocyte death is poorly understood. The present study was aimed to investigate the cardioprotective role of salidroside and the underlying mechanisms in hypoxia-induced cardiomyocyte death. Cardiomyocytes pretreated with or without salidroside for 24 It were exposed to hypoxic condition for 6 h and then cell viability, necrosis, apoptosis, the expressions of HIF-1 alpha and VEGF were investigated. Pretreatment with salidroside markedly attenuated hypoxia-induced cell viability loss, cell necrosis and apoptosis in a dose-dependent manner. Mechanistically, pretreatment with salidroside up-regulated the HIF-1 alpha protein expression and induced its translocation. Moreover, the level of VEGF, a downstream target of HIF, was significantly increased in parallel with the level of HIF-1 alpha following pretreatment with salidroside. However, 2-methoxyestradiol (2-ME2), a HIF-1 alpha inhibitor, attenuated the protection of salidroside and blocked the increase of HIF-1 alpha and VEGF. These data indicated that salidroside has protective effect against hypoxia-induced cardiomyocytes necrosis and apoptosis by increasing HIF-1 alpha expression and subsequently up-regulating VEGF levels. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.