Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK/NF-κB/NLRP3 signaling pathway in AGEs-induced HUVECs
Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK/NF-κB/NLRP3 signaling pathway in AGEs-induced HUVECs
复制标题
红景天苷通过调节 AGE 诱导的 HUVEC 中的 AMPK/NF-κB/NLRP3 信号通路改善内皮炎症和氧化应激
DOI：
10.1016/j.ejphar.2019.172797
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发表时间：
2020-01-15
影响因子：
5
通讯作者：
Wei, Lian-bo
中科院分区：
文献类型：
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作者：
Hu, Rong;Wang, Ming-qing;Wei, Lian-bo
内皮功能障碍在糖尿病血管功能障碍中起重要作用。晚期糖基化终产物(AGEs)的产生可诱导炎症和氧化应激，在内皮功能障碍中起关键作用。红景天苷是红景天中的主要活性成分，对血管疾病具有保护作用。为探讨红景天苷对糖尿病血管内皮细胞功能障碍的影响及其机制，建立了AGEs诱导的人脐静脉内皮细胞(HUVECs)体外模型。检测细胞存活率、细胞凋亡率、促炎细胞因子和氧化生物标志物，以确定红景天苷10、50和100mM剂量对AGEs诱导的人脐静脉内皮细胞的影响。此外，RNAseq和生物信息学分析被用来寻找红景天苷的潜在机制。结果表明，红景天苷对AGEs诱导的人脐静脉内皮细胞有促进细胞活力和明显减轻细胞凋亡的作用。此外，红景天苷还能显著降低AGEs诱导的促炎细胞因子TNF-α、IL-1β和IL-6的水平，抑制AGEs诱导的VCAM-1和ICAM-1的表达。此外，红景天苷还能促进AGEs诱导的HUVECs超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSHPx)水平，抑制细胞内活性氧(ROS)和丙二醛(MDA)的产生。重要的是，红景天苷通过激活AMPK磷酸化，抑制NF-kappa B p65和NLRP3炎症体的激活，减轻内皮细胞炎症和氧化应激。因此，我们使用了化合物C，一个公认的AMPK抑制剂，进一步证明了这一机制。有趣的是，红景天苷产生的现象被废除了。我们的研究结果表明，红景天苷可部分通过AMPK/NF-kappa B/NLRP3信号通路减轻AGEs诱导的内皮炎症和氧化应激。
Endothelial dysfunction plays important roles in vascular dysfunction under diabetic conditions. The generation of advanced glycation end products (AGEs), which can induce inflammation and oxidative stress, is pivotal in endothelial dysfunction. Salidroside, a major active compound in Rhodiola rosea, exerts protective effects against vascular diseases. To study the effects and mechanism of salidroside in diabetes-induced vascular endothelial dysfunction, an in vitro model was established with AGEs-induced human umbilical vein endothelial cells (HUVECs). Then, cell viability, cell apoptosis, pro-inflammatory cytokines and oxidative biomarkers were tested to determine the effects of salidroside at 10, 50 and 100 mu M doses on AGEs induced HUVECs. Additionally, RNASeq and bioinformatics analyses were used to search for the underlying mechanism of salidroside. The results showed that salidroside promoted cell viability and significantly alleviated cell apoptosis in AGEs-induced HUVECs. Furthermore, salidroside remarkably decreased the levels of the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IL-6 and impeded the expression of VCAM-1 and ICAM-1 induced by AGEs. Additionally, salidroside promoted superoxide dismutase (SOD) activity and increased catalase (CAT) and glutathione peroxidase (GSHPx) levels while inhibiting the intracellular generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in AGEs-induced HUVECs. Importantly, salidroside alleviated endothelial inflammation and oxidative stress by activating AMPK phosphorylation and inhibiting NF-kappa B p65 and NLRP3 inflammasome activation. Therefore, we used compound C, an accepted AMPK inhibitor, to further demonstrate the mechanism. Interestingly, the phenomenon produced by salidroside was abolished. Our findings suggest that salidroside ameliorates AGEs-induced endothelial inflammation and oxidative stress, partially via the AMPK/NF-kappa B/NLRP3 signaling pathway.