Tanshinone IIA Sodium sulfonate regulates antioxidant system, inflammation, and endothelial dysfunction in atherosclerosis by downregulation of CLIC1
Tanshinone IIA Sodium sulfonate regulates antioxidant system, inflammation, and endothelial dysfunction in atherosclerosis by downregulation of CLIC1
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丹参酮 IIA 磺酸钠通过下调 CLIC1 调节动脉粥样硬化中的抗氧化系统、炎症和内皮功能障碍
DOI：
10.1016/j.ejphar.2017.09.047
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发表时间：
2017-11
影响因子：
5
通讯作者：
Dezhao Lu
中科院分区：
文献类型：
--
作者：
Ji Zhu;Yingling Xu;Guangyan Ren;Xiao Hu;Cui Wang;Zhen Yang;Zhuoyu Li;Wei Mao;Dezhao Lu
研究背景丹参酮Ⅱ A磺酸钠（Tanshinone Ⅱ A Sodium sulfonate，STS）具有抗氧化、抗炎等作用，被中医药临床用于心血管疾病的治疗。细胞内氯离子通道1（CLIC 1）参与氧化应激和炎症的调节。本研究调查是否CLIC 1介导的心脏保护作用的STS.MethodsSTS被用来治疗动脉粥样硬化（AS）诱导喂养载脂蛋白E-缺陷（ApoE-/-）小鼠与高脂肪，胆固醇丰富的饮食。此外，正常和CLIC 1-/-人脐静脉内皮细胞在H2 O2作用12 h后，用STS处理。通过分析活性氧（ROS）和丙二醛（MDA）水平来确定氧化状态。采用ELISA、qRT-PCR和Western blot检测TNF-α、IL-6、ICAM-1和VCAM-1的水平。CLIC 1细胞定位用免疫荧光法检测。结果STS治疗后动脉粥样硬化病变面积减少了3.5倍（P = 0.001）。同时，STS可降低动脉粥样硬化小鼠MDA生成（13.6%，P = 0.008），提高SOD活性（113.6%，P = 0.008），降低TNF-α（38.6%，P = 0.008）和IL-6（43.0%，P = 0.03）水平，下调CLIC 1、ICAM-1和VCAM-1的表达。体外实验进一步证实了STS具有剂量依赖性的抗氧化和抗炎作用。此外，CLIC 1耗竭消除STS介导的ROS和MDA产生的减少在HUVEC细胞。此外，STS抑制CLIC 1膜转位和氯离子concentration.ConclusionThe抗氧化，抗炎症性能的STS预防AS是通过其抑制CLIC 1的表达和膜转位。
BackgroundTanshinone IIA Sodium sulfonate (STS) is clinically used for treating cardiovascular diseases in Traditional Chinese Medicine due to its antioxidation and anti-inflammation activities. Intracellular chloride channel 1 (CLIC1) participates in the regulation of oxidative stress and inflammation. This study investigates whether CLIC1 mediates the cardioprotective effects of STS.MethodsSTS were used to treat atherosclerosis (AS) induced by feeding Apolipoprotein E-deficient (ApoE-/-) mice with a high-fat, cholesterol-rich diet. In addition, normal andCLIC1-/-human umbilical vein endothelial cells were treated with STS after exposure to H2O2for 12 h. The oxidative status was determined by analyzing reactive oxygen species(ROS) and malondialdehyde (MDA) levels. ELISA, qRT-PCR and Western blot were used to determine the levels of TNF-α, IL-6, ICAM-1 and VCAM-1. CLIC1 cellular localization was examined by immunofluorescence. Chloride ion concentration was detected with chloride ion quenchers (MQAE).ResultsSTS treatment decreased atherosclerotic lesion area by 3.5 times (P = 0.001) in vivo. Meanwhile, STS reduced MDA production (13.6%, P = 0.008), increased SOD activity (113.6%, P = 0.008), decreased TNF-α (38.6%, P = 0.008) and IL-6 (43.0%, P = 0.03) levels, and downregulated the expression of CLIC1, ICAM-1, and VCAM-1 in the atherosclerotic mice. The dose-dependent anti-oxidative and anti-inflammatory effects of STS were further confirmed in vitro. Furthermore, CLIC1 depletion abolished the STS-mediated decrease of ROS and MDA production in HUVEC cells. Additionally, STS inhibited both CLIC1 membrane translocation and chloride ion concentration.ConclusionThe anti-oxidant, and anti-inflammation properties of STS in preventing AS is mediated by its inhibition of CLIC1 expression and membrane translocation.
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影响因子：
9.5
作者：
Zhang C
通讯作者：
Zhang C
影响因子：
2.5
作者：
Haiyan Zhang;M. Long;Zhiwen Wu;Xu Han;Yichao Yu
通讯作者：
Haiyan Zhang;M. Long;Zhiwen Wu;Xu Han;Yichao Yu
影响因子：
4.8
作者：
Gong, Zhenwei;Huang, Cheng;Zang, Ying Qin
通讯作者：
Zang, Ying Qin
影响因子：
5
作者：
Chen, Wenying;Tang, Futian;Liu, Peiqing
通讯作者：
Liu, Peiqing
影响因子：
4.8
作者：
Valenzuela, SM;Martin, DK;Breit, SN
通讯作者：
Breit, SN