Resveratrol attenuates hydrogen peroxide-induced aging through upregulation of autophagy in human umbilical vein endothelial cells
Resveratrol attenuates hydrogen peroxide-induced aging through upregulation of autophagy in human umbilical vein endothelial cells
复制标题
白藜芦醇通过上调人脐静脉内皮细胞自噬来减轻过氧化氢引起的衰老
DOI：
10.2147/dddt.s179894
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Wu, Saizhu
中科院分区：
文献类型：
--
作者：
Du, Ligen;Chen, Enping;Wu, Saizhu
目的：白藜芦醇（Resveratrol，RESV; trans-3，5，4 '-trihydroxystilbene）是一种治疗老年动脉粥样硬化性疾病的新药物。然而，RESV对细胞衰老的影响及其潜在机制仍不清楚。材料与方法：将人脐静脉内皮细胞（HUVECs）分为4组：对照组、单纯过氧化氢（H2 O2）干预组、H2 O2 + RESV预处理组、H2 O2 + 3-甲基腺嘌呤（3-MA）+ RESV预处理干预组。通过细胞计数试剂盒-8测定法评价细胞活力。超氧化物歧化酶（SOD）活性和细胞内活性氧（ROS）水平进行了测试，使用商业试剂盒。免疫组化法检测衰老相关β-半乳糖苷酶活性。用Western blotting检测细胞衰老相关和自噬相关标志物（包括磷酸化Rb（p-Rb）、LC 3和p62）的表达水平，用10 μ M RESV预处理可提高细胞活力和SOD水平。衰老相关β-半乳糖苷酶的显着较高的阳性率和细胞内ROS水平的增加，在H2 O2处理组逆转与10 μ M RESV治疗。与H2 O2处理组相比，10 μ M RESV可通过调节p-Rb、LC 3和p62水平上调自噬。结论：RESV可能通过上调自噬来逆转和延缓HUVECs的衰老过程，有望成为治疗年龄相关性动脉粥样硬化疾病的候选药物。
Purpose: Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene) has emerged as a potential new therapeutic for age-related atherosclerotic diseases. However, the effect of RESV on cellular aging and its underlying mechanisms remain unknown. Therefore, the aim of this study was to examine whether RESV can delay cellular aging through upregulation of autophagy.Materials and methods: Human umbilical endothelial vein cells (HUVECs) were divided into four groups: the control group, and the hydrogen peroxide (H2O2) alone, H2O2 + RESV pretreatment, and H2O2 + 3-methyladenine (3-MA) + RESV pretreatment intervention groups. The cell viability was evaluated by a cell counting kit-8 assay. Superoxide dismutase (SOD) activity and intracellular reactive oxygen species (ROS) levels were tested using commercial kits. Senescence-related beta-galactosidase activities were detected by immunohistochemical staining. The expression levels of aging-related and autophagyrelated markers, including phosphorylated Rb (p-Rb), LC3, and p62, with or without RESV were measured by Western blotting.Results: Pretreatment with 10 mu M RESV increased the cell viability and SOD levels. The remarkably higher positive rate of senescence-associated beta-galactosidase and increased intracellular ROS levels in the H2O2 treatment group were reversed by treatment with 10 mu M RESV. As compared to the H2O2 treatment group, 10 mu M RESV could upregulate autophagy through the regulation of p-Rb, LC3, and p62 levels. The anti-aging effect of RESV via an autophagy regulation mechanism was further confirmed by the suppression of these effects with 3-MA treatment.Conclusion: RESV may reverse and delay the aging process of HUVECs via upregulation of autophagy and could be a candidate therapeutic for age-related atherosclerotic diseases.