Naringenin Exerts Cardiovascular Protective Effect in a Palmitate-Induced Human Umbilical Vein Endothelial Cell Injury Model via Autophagy Flux Improvement
Naringenin Exerts Cardiovascular Protective Effect in a Palmitate-Induced Human Umbilical Vein Endothelial Cell Injury Model via Autophagy Flux Improvement
复制标题
柚皮素通过改善自噬通量在棕榈酸酯诱导的人脐静脉内皮细胞损伤模型中发挥心血管保护作用
DOI：
10.1002/mnfr.201900601
复制
发表时间：
2019
影响因子：
5.2
通讯作者：
Yang Yining
中科院分区：
文献类型：
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作者：
Zhao Qiang;Yang Hongyan;Liu Fen;Luo Junyi;Zhao Qian;Li Xiaomei;Yang Yining
东莨菪碱棕榈酸（PA）通过促进内皮功能障碍而有助于心血管疾病的发病机制，而柑橘中最丰富的柚皮素已被证明对人类心血管系统发挥多种有益作用。本研究探讨了柚皮素是否能阻止PA诱导的人脐静脉内皮细胞（HUVECs）凋亡。方法和结果PA治疗至少24 h会导致细胞活力、氧化应激、自噬通量紊乱和HUVECs凋亡水平明显下降。柚皮素增强PA处理的HUVEC的活力，此外，通过清除ROS和增加SOD 2水平和GPx活性有效降低氧化应激。自噬通量受到柚皮素的保护，如PA诱导的HUVEC中LC 3B-II/I比率、p62表达水平和自噬体数量的降低以及自溶酶体数量的增加所证明的。这些作用被氧化应激抑制剂N-乙酰半胱氨酸和自噬抑制剂氯喹证实。结论柚皮素对自噬的保护作用可能是通过JNK通路实现的，JNK抑制剂SP 600125的应用证实了这一点。
ScopePalmitic acid (PA) contributes to the pathogenesis of cardiovascular disease by promoting endothelial dysfunction, while naringenin, most abundant in oranges, has been shown to exert multiple beneficial effects on the human cardiovascular system. This study explores whether naringenin prevents PA‐induced apoptosis in human umbilical vein endothelial cells (HUVECs).Methods and ResultsTreatment of PA for at least 24 h causes observable decrease in levels of cell viability, oxidative stress, disorder of autophagy flux, and apoptosis in HUVECs. Naringenin enhances the viability of the PA‐treated HUVECs and, additionally, effectively decreases oxidative stress by scavenging ROS, and increasing the SOD2 level and GPx activity. Autophagy flux is protected by naringenin, as evidenced by the decreases in the ratio of LC3B‐II/I, expression level of p62 and number of autophagosomes, and the increase in the number of autolysosomes in the PA‐induced HUVECs. These effects are confirmed by the oxidative stress inhibitorN‐acetyl‐cysteine and autophagy inhibitor chloroquine. The molecular data indicate that the protective effects of naringenin on autophagy flux may also be regulated via the JNK pathway, as verified via the application of JNK inhibitor SP600125.ConclusionThese findings provide a possible mechanism by which naringenin prevents endothelial dysfunction and cardiovascular diseases.