Beneficial effects of evodiamine on P2X4-mediated inflammatory injury of human umbilical vein endothelial cells due to high glucose

Beneficial effects of evodiamine on P2X4-mediated inflammatory injury of human umbilical vein endothelial cells due to high glucose
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吴茱萸碱对高糖引起的P2X(4)介导的人脐静脉内皮细胞炎症损伤的有益作用

DOI:
10.1016/j.intimp.2015.08.020
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发表时间:
2015-10-01
影响因子:
5.6
通讯作者:
Liang, Shangdong
Liang, Shangdong
中科院分区:
医学2区
文献类型:
--
作者:
Lv, Qiulan;Xue, Yun;Liang, Shangdong

文献摘要

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据报道吴茱萸碱具有抗炎和抗伤害作用,但其潜在机制仍有待确定。 P2X(4) 受体 (P2X(4)R) 是 ATP 受体的一种亚型,在疼痛、炎症和免疫反应中发挥重要作用。我们的目的是研究吴茱萸碱是否对慢性高血糖介导的内皮炎症损伤具有有益作用。我们发现,高糖培养人脐静脉内皮细胞(HUVEC)显着增加HUVEC中P2X(4)受体的表达、胞质Ca2+浓度和细胞内活性氧(ROS),同时减少一氧化氮(NO);吴茱萸碱可以逆转这些影响。高葡萄糖还显着增加促炎激活剂(NF-κB)和TNFR-α的表达,同时伴随着P2X(4)R水平的升高。吴茱萸碱能够下调升高的 NF-kappa B、TNFR-α、P2X(4)R 和 ROS,并上调降低的 NO。因此吴茱萸碱可能通过抑制P2X(4)R信号通路对高糖挑战的HUVEC发挥抗炎活性,表现出保护HUVEC免受糖毒性的有益能力。 (C) 2015 Elsevier B.V. 保留所有权利。
Evodiamine has been reported to exhibit anti-inflammatory and anti-nociceptive effects, but the underlying mechanisms remain to be defined. P2X(4) receptor (P2X(4)R) is a subtype of ATP receptors and plays important roles In pain, inflammatory and immune responses. We aimed to investigate whether evodiamine has beneficial effects on endothelial inflammatory injury mediated by chronic high glucose condition. We found that culturing human umbilical vein endothelial cells (HUVECs) with high glucose significantly increased the expression of P2X(4) receptor in HUVECs, cytosolic Ca2+ concentrations and intracellular reactive oxygen species (ROS) while decreasing nitric oxide (NO); these effects could be reversed by evodiamine. High glucose also significantly increased the expression of the pro-inflammatory activators (NF-kappa B) and TNFR-alpha, which was accompanied by the elevation of P2X(4)R levels. Evodiamine was able to down-regulate the elevated NF-kappa B, TNFR-alpha, P2X(4)R and ROS, and up-regulate the decreased NO. Thus the evodiamine may exert the anti-inflammation activity on high-glucose challenge HUVEC via suppressing the P2X(4)R signaling pathway, exhibiting beneficial ability to protect HUVECs from glucotoxicity. (C) 2015 Elsevier B.V. All rights reserved.