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用掺钆氧化铈减少活性氧积累缓解动脉粥样硬化。

Reduction of Reactive Oxygen Species Accumulation Using Gadolinium-Doped Ceria for the Alleviation of Atherosclerosis.

机构信息

Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an 710072, China.

出版信息

ACS Appl Mater Interfaces. 2023 Mar 1;15(8):10414-10425. doi: 10.1021/acsami.2c20492. Epub 2023 Feb 19.

Abstract

Atherosclerosis is a common cardiovascular disease with increasing morbidity and mortality. The pathogenesis of atherosclerosis is strongly related to endothelial dysfunction, which is induced by severe oxidative stress damage derived from reactive oxygen species (ROS). Thus, ROS plays a critical role in the pathogenesis and progression of atherosclerosis. In this work, we demonstrated that the gadolinium doping of CeO (Gd/CeO) nanozymes as effective ROS scavengers delivered high performance for antiatherosclerosis. It was found that the chemical doping of Gd promoted the surface proportion of Ce in the nanozymes and thereby enhanced the overall ROS scavenging ability. In vitro and in vivo experiments unambiguously showed that the Gd/CeO nanozymes efficiently scavenged harmful ROS at the cellular and histological levels. Further, Gd/CeO nanozymes were demonstrated to significantly reduce vascular lesions by reducing lipid accumulation in macrophage and decreasing inflammatory factor levels, thereby inhibiting the exacerbation of atherosclerosis. Moreover, Gd/CeO can serve as -weighted magnetic resonance imaging contrast agents, which can generate sufficient contrast to distinguish the location of plaque during living imaging. Through those efforts, Gd/CeO may serve as a potential diagnostic and treatment nanomedicine for the ROS-induced atherosclerosis.

摘要

动脉粥样硬化是一种常见的心血管疾病,发病率和死亡率不断上升。动脉粥样硬化的发病机制与内皮功能障碍密切相关,内皮功能障碍是由活性氧(ROS)引起的严重氧化应激损伤所致。因此,ROS 在动脉粥样硬化的发病机制和进展中起着关键作用。在这项工作中,我们证明了作为有效 ROS 清除剂的氧化铈(CeO)纳米酶的钆掺杂(Gd/CeO)具有出色的抗动脉粥样硬化性能。研究发现,Gd 的化学掺杂促进了纳米酶中 Ce 的表面比例,从而增强了整体 ROS 清除能力。体外和体内实验明确表明,Gd/CeO 纳米酶通过在细胞和组织学水平上清除有害的 ROS,有效地清除了 ROS。此外,Gd/CeO 纳米酶通过减少巨噬细胞中的脂质积累和降低炎症因子水平,显著减少了血管损伤,从而抑制了动脉粥样硬化的恶化。此外,Gd/CeO 可用作磁共振成像的造影剂,可产生足够的对比,在活体成像中区分斑块的位置。通过这些努力,Gd/CeO 可能成为一种潜在的诊断和治疗动脉粥样硬化的纳米医学方法。

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