Salidroside attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2a receptor related mitochondria-dependent apoptosis pathway
Salidroside attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2a receptor related mitochondria-dependent apoptosis pathway
复制标题
红景天苷通过腺苷 A2a 受体相关线粒体依赖性细胞凋亡途径减轻慢性缺氧诱导的肺动脉高压
DOI：
10.1016/j.yjmcc.2015.03.005
复制
发表时间：
2015-05-01
影响因子：
5
通讯作者：
Wang, Liangxing
中科院分区：
文献类型：
--
作者：
Huang, Xiaoying;Zou, Lizhen;Wang, Liangxing
肺动脉高压（PAH）是以肺动脉平滑肌细胞（PASMCs）过度增殖和凋亡抵抗为主要特征的肺动脉重构。红景天苷是一种从玫瑰红景天中分离出来的活性成分，被认为对多环芳烃具有保护作用。然而，红景天苷在多环芳烃中的作用尚未得到系统研究，其潜在机制尚不清楚。为探讨红景天苷对肺动脉高压（PAH）的治疗作用，采用小鼠慢性缺氧模型，按递增剂量（0、16、32、64 mg/kg）给予红景天苷。红景天苷治疗后，慢性缺氧引起的右心室肥厚和肺动脉重构减轻，提示红景天苷对PAH具有保护作用。为探讨其可能的机制，本研究在体内和体外检测了红景天苷处理后PASMCs在缺氧条件下的凋亡情况，并检测了细胞凋亡相关因子Bax、Bcl-2、细胞色素C和caspase 9的表达。结果表明，红景天苷至少部分地通过依赖于多巴胺的途径逆转缺氧诱导的细胞凋亡抵抗。红景天苷还能上调缺氧小鼠肺组织和体外培养PASMCs腺苷A（2a）受体（A（2a）R）的表达。综上所述，红景天苷可通过A2 aR相关的线粒体依赖性途径促进PASMCs凋亡，从而减轻慢性缺氧诱导的肺动脉高压。(C)2015作者爱思唯尔有限公司出版
Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial remodeling mainly due to excess cellular proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Salidroside, an active ingredient isolated from Rhodiola rosea is proposed to exert protective effects against PAH. However, the function of salidroside in PAH has not been investigated systematically and the underlying mechanisms are not clear. To investigate the effects of salidroside on PAH, the mice in chronic hypoxia model of PAH were given by an increasing concentration of salidroside (0, 16 mg/kg, 32 mg/kg, and 64 mg/kg). After salidroside treatment, the chronic hypoxia-induced right ventricular hypertrophy and pulmonary arterial remodeling were attenuated, suggesting a protective role played by salidroside in PAH. To explore the potential mechanisms, the apoptosis of PASMCs after salidroside treatment under hypoxia conditions were determined in vivo and in vitro, and also the mitochondria-dependent apoptosis factors, Bax, Bcl-2, cytochrome C, and caspase 9 were examined. The results revealed that salidroside reversed hypoxia-induced cell apoptosis resistance at least partially via a mitochondria-dependent pathway. In addition, salidroside upregulated the expression of adenosine A(2a) receptor (A(2a)R) in lung tissues of mice and in PASMCs in vitro after hypoxia exposure. Combined the evidence above, we conclude that salidroside can attenuate chronic hypoxia-induced PAH by promoting PASMCs apoptosis via an A2aR related mitochondria dependent pathway. (C) 2015 The Authors. Published by Elsevier Ltd.