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释放硫化氢的阿司匹林可增强细胞抗氧化损伤和抗炎的能力。

Hydrogen sulphide-releasing aspirin enhances cell capabilities of anti-oxidative lesions and anti-inflammation.

作者信息

Zhao An-Sha, Zou Dan, Wang Hao-Hao, Han Xiao, Yang Ping, Huang Nan

机构信息

Key Laboratory for Advanced Technologies of Materials, Ministry of Education; School of Material Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan Province, China.

出版信息

Med Gas Res. 2019 Jul-Sep;9(3):145-152. doi: 10.4103/2045-9912.266990.

Abstract

Hydrogen sulphide (HS) has been considered as a toxic gas for a long time till new researches discovered the endogenous HS effects on physiological and pathological processes. In virtue of HS's effects on cellular redox imbalance and aspirin's good anticoagulation property, exogenous HS donors, such as HS-releasing aspirin (ACS14), have been explored to attenuate side effects of aspirin on gastrointestinal mucosal damage. However, existing researches mainly focus on the antithrombotic effects. Considering HS role in angiogenesis and vascular-protection progress, we herein focused on if ACS14 further has the ability to attenuate oxidative lesion and inflammation in human umbilical vein endothelial cells (HUVECs) and macrophages. In this study, we synthesized ACS14 by 5-(4-methoxyphenyl)-1,2-dithiole-3-thione and o-acetylsalicylic acid (aspirin), and the obtained compounds showed the ability to release HS. Our data illustrated that both aspirin and ACS14 had good cytocompatibility, and could support the proliferation of HUVECs. And, ACS14 was found to be able to promote 1.6 folds increase compared to aspirin. HS released from ACS14 was detected inside cells, wherein H2S fluorescence intensity increased twofold in 5 μM and 10 μM ACS14 groups than 1 μM group. Owing to reactive oxygen species inside cells being obviously decreased in ACS14 group, the apoptosis rate of HUVEC herein was reduced as low as 1.6% from 60% of blank group. Meanwhile, the tumour necrosis factor alpha release in macrophage was also declined by 15% in ACS14 groups than the others. Basically, the ACS14 we obtained had the cyto-protective and anti-inflammatory capabilities. Potential applications for vascular intima repair in atherosclerosis are further expected.

摘要

长期以来,硫化氢(HS)一直被视为一种有毒气体,直到新的研究发现内源性HS对生理和病理过程的影响。鉴于HS对细胞氧化还原失衡的影响以及阿司匹林良好的抗凝特性,人们探索了外源性HS供体,如释放HS的阿司匹林(ACS14),以减轻阿司匹林对胃肠道黏膜损伤的副作用。然而,现有研究主要集中在抗血栓形成作用上。考虑到HS在血管生成和血管保护过程中的作用,我们在此关注ACS14是否进一步具有减轻人脐静脉内皮细胞(HUVECs)和巨噬细胞氧化损伤和炎症的能力。在本研究中,我们通过5-(4-甲氧基苯基)-1,2-二硫醇-3-硫酮与邻乙酰水杨酸(阿司匹林)合成了ACS14,所得化合物显示出释放HS的能力。我们的数据表明,阿司匹林和ACS14都具有良好的细胞相容性,并且能够支持HUVECs的增殖。而且,发现ACS14相比阿司匹林能够促进1.6倍的增加。在细胞内检测到从ACS14释放的HS,其中5μM和10μM ACS14组中的H2S荧光强度比1μM组增加了两倍。由于ACS14组中细胞内活性氧明显减少,HUVECs的凋亡率从空白组的60%降低至低至1.6%。同时,ACS14组中巨噬细胞中肿瘤坏死因子α的释放也比其他组下降了15%。基本上,我们获得的ACS14具有细胞保护和抗炎能力。进一步期望其在动脉粥样硬化血管内膜修复中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43fc/6779009/1345a8e20aa7/MGR-9-145-g001.jpg

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