Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice
Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice
复制标题
氢分子可稳定低密度脂蛋白受体敲除小鼠的动脉粥样硬化斑块。
DOI：
10.1016/j.freeradbiomed.2015.06.018
复制
发表时间：
2015-10-01
影响因子：
7.4
通讯作者：
Qin, Shucun
中科院分区：
文献类型：
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作者：
Song, Guohua;Zongh, Chuanlong;Qin, Shucun
氢(H-2)可减轻小鼠模型动脉粥样硬化的发展。我们的目的是研究H-2对动脉粥样硬化斑块稳定性的影响。低密度脂蛋白受体基因敲除(LDLR-/-)小鼠喂饲致动脉粥样硬化的饮食，每天服用H-2和/或辛伐他汀。体外研究是在氧化型低密度脂蛋白(ox-LDL)刺激的巨噬细胞来源的泡沫细胞模型中进行的，H-2处理或不处理。H-2或辛伐他汀通过增加胶原水平以及降低斑块中的巨噬细胞和脂质水平显著增强斑块的稳定性。斑块中结缔组织细胞数量的减少和调节性T细胞数量的增加进一步支持了H-2或辛伐他汀的稳定作用。此外，H-2治疗降低了血清OX-LDL水平和斑块中的细胞凋亡，同时抑制了内质网应激反应(MRS)，并减少了活性氧物种(ROS)在主动脉中的积聚。在体外，与ERS抑制剂4-苯基丁酸一样，H-2也能抑制OX[DL-或衣霉素(ERS诱导剂)诱导的ERS反应和细胞凋亡。此外，与ROS清除剂N-乙酰半胱氨酸一样，H-2可抑制氧化低密度脂蛋白或Cu2+(ROS诱导剂)诱导的细胞活力下降和细胞内ROS增加。此外，H-2增加了Nrt2(一种抗氧化信号的重要因子)的激活，Nrt2小干扰RNA取消了H-2对氧化低密度脂蛋白诱导的细胞ROS产生的保护作用。H-2对巨噬细胞源性泡沫细胞凋亡的抑制作用可能是通过抑制ERS途径的激活和激活Nrf2抗氧化途径来实现的，从而可能导致动脉粥样硬化斑块稳定性的改善。(C)爱思唯尔公司出版的2015年。
Hydrogen (H-2) attenuates the development of atherosclerosis in mouse models. We aimed to examine the effects of H-2 on atherosclerotic plaque stability. Low-density lipoprotein receptor-knockout (LDLR-/-) mice fed an atherogenic diet were dosed daily with H-2 and/or simvastatin. In vitro studies were carried out in an oxiclized-LDL (ox-LDL)-stimulated macrophage-derived foam cell model treated with or without H-2. H-2 or simvastatin significantly enhanced plaque stability by increasing levels of collagen, as well as reducing macrophage and lipid levels in plaques. The decreased numbers of denclritic cells and increased numbers of regulatory T cells in plaques further supported the stabilizing effect of H-2 or simvastatin. Moreover, H-2 treatment decreased serum ox-LDL level and apoptosis in plaques with concomitant inhibition of endoplasmic reticulum stress MRS) and reduction of reactive oxygen species (ROS) accumulation in the aorta. In vitro, like the ERS inhibitor 4-phenylbutyric acid, H-2 inhibited ox[DL- or tunicamycin (an ERS inducer)-induced ERS response and cell apoptosis. In addition, like the ROS scavenger N-acetylcysteine, H-2 inhibited ox-LDL- or Cu2+ (an ROS inducer)-induced reduction in cell viability and increase in cellular ROS. Also, H-2 increased Nrt2 (NF-E2-related factor-2, an important factor in antioxidant signaling) activation and Nrt2 small interfering RNA abolished the protective effect of H-2 on ox-LDL-induced cellular ROS production. The inhibitory effects of H-2 on the apoptosis of macrophagederived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability. (C)2015 Published by Elsevier Inc.