Sevoflurane pretreatment attenuates TNF-α-induced human endothelial cell dysfunction through activating eNOS/NO pathway
Sevoflurane pretreatment attenuates TNF-α-induced human endothelial cell dysfunction through activating eNOS/NO pathway
复制标题
七氟烷预处理通过激活 eNOS/NO 通路减轻 TNF-α 诱导的人内皮细胞功能障碍
DOI：
10.1016/j.bbrc.2015.03.126
复制
发表时间：
2015-05-08
影响因子：
3.1
通讯作者：
Ruan, Wei
中科院分区：
文献类型：
--
作者：
Li, Suobei;Xu, Junmei;Ruan, Wei
氧化应激和炎症引起的内皮功能障碍在心血管疾病的发病机制中起着重要作用。麻醉剂七氟醚通过其抗炎作用在全身炎症反应综合征和缺血再灌注损伤等多种病理过程中发挥细胞保护作用，但其机制尚不清楚。我们假设七氟醚可通过促进内皮依赖性一氧化氮(NO)的产生来保护肿瘤坏死因子(TNF)-α诱导的内皮功能障碍。原代培养的人脐静脉内皮细胞(HUVECs)经不同浓度(0.5、1.5、2.5最低肺泡浓度，MAC)的七氟醚预处理30min后，再加入10 ng/mL七氟醚刺激4h，可显著降低TNF-α诱导的VCAM-1、ICAM-1、I-kappaBα和核因子-kappaB的活化，并阻断白细胞与HUVECs的黏附。同时，七氟醚(1.5和2.5MAC)显著诱导内皮型一氧化氮合酶(ENOS)磷酸化，并增加细胞内和细胞培养上清液中的NO水平。非特异性一氧化氮合酶抑制剂L精氨酸甲酯(NAME)可阻断七氟烷的上述细胞保护作用。总而言之，这些数据表明，七氟醚通过激活eNOS/NO途径和抑制核因子-kappa B(C)2015年，对肿瘤坏死因子-α诱导的血管内皮功能障碍具有保护作用。由Elsevier Inc.出版。这是一篇CC BY-NC-ND许可下的开放获取文章。
Endothelial dysfunction induced by oxidative stress and inflammation plays a critical role in the pathogenesis of cardiovascular diseases. The anesthetic sevoflurane confers cytoprotective effects through its anti-inflammatory properties in various pathologies such as systemic inflammatory response syndrome and ischemic-reperfusion injury but mechanism is unclear. We hypothesized that sevoflurane can protect against tumor necrosis factor (TNF)-alpha-induced endothelial dysfunction through promoting the production of endothelium-dependent nitric oxide (NO). Primary cultured human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations (0.5, 1.5 and 2.5 minimum alveolar concentration, MAC) of sevoflurane for 30 min before TNF-alpha (10 ng/mL) stimulation for 4 h. Sevoflurane pretreatment significantly reduced TNF-alpha-induced VCAM-1, ICAM-1, I kappa B alpha, and NF-kappa B activation, and blocked leukocytes adhesion to HUVECs. Meanwhile, sevoflurane (1.5 and 2.5 MAC) significantly induced endothelial nitric oxide synthase (eNOS) phosphorylation and enhanced NO levels both intracellularly and in the cell culture medium. All these cytoprotective effects of sevoflurane were abrogated by NG-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor. Collectively, these data indicate that sevoflurane protects against TNF-alpha -induced vascular endothelium dysfunction through activation of eNOS/NO pathway and inhibition of NF-kappa B. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.