Yu Fu-Chao, Yuan Chu-Xiao, Tong Jia-Yi, Zhang Guang-Hao, Zhou Fang-Ping, Yang Fang
Medical School, Southeast University, Nanjing, Jiangsu, 210096, China; Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu, 210096, China.
State Key Laboratory of Bioelectronics and Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Biochem Biophys Res Commun. 2018 Apr 15;498(4):1016-1021. doi: 10.1016/j.bbrc.2018.03.106. Epub 2018 Mar 17.
Intermittent hypoxia (IH) induced by obstructive sleep apnea (OSA) is the key factor in oxidative stress and the concomitant inflammation of endothelial cells (ECs). In recent years, the lipid sphingosine-1-phosphate (S1P) has been reported to probably play a central role in inflammatory diseases. However, its role in IH-induced endothelial injury remains uncertain. In this study, we investigated the IH-induced ECs inflammation and apoptosis, as well as the role of S1P in both. First, human umbilical vein endothelial cells (HUVECs) were treated with IH to explore the mechanism of S1P and S1P microbubbles (S1P-MBs) in HUVECs with altered function. The intracellular reactive oxygen species (ROS) significantly increased after IH treatment, which further resulted in the increased efficiency of cell apoptosis. Following the S1P and S1P-MBs treatments, the lower Bax protein and Cyt c protein levels in HUVECs indicated the protective effects of S1P for CIH-induced ECs injury. The reason may be that the enhanced expression levels of Gα and S1P receptor 1 in S1P and S1P-MBs treatment groups could actively increase intracellular p-Akt and p-eNOS protein levels, which counteract the increased ROS secondary to inflammation from IH. Therefore, the Akt/eNOS signaling pathway induced by S1P may be important in protecting IH-induced ECs injury. Furthermore, the S1P-MBs may be designed as a novel S1P dosage formulation to protect the body from the ECs injuries in the future.
阻塞性睡眠呼吸暂停（OSA）引起的间歇性缺氧（IH）是氧化应激以及内皮细胞（ECs）随之发生炎症的关键因素。近年来，有报道称脂质鞘氨醇-1-磷酸（S1P）可能在炎症性疾病中起核心作用。然而，其在IH诱导的内皮损伤中的作用仍不确定。在本研究中，我们调查了IH诱导的ECs炎症和凋亡，以及S1P在两者中的作用。首先，用IH处理人脐静脉内皮细胞（HUVECs），以探索S1P和S1P微泡（S1P-MBs）在功能改变的HUVECs中的作用机制。IH处理后细胞内活性氧（ROS）显著增加，这进一步导致细胞凋亡效率提高。在S1P和S1P-MBs处理后，HUVECs中较低的Bax蛋白和Cyt c蛋白水平表明S1P对CIH诱导的ECs损伤具有保护作用。原因可能是S1P和S1P-MBs处理组中Gα和S1P受体1的表达水平增强，可积极提高细胞内p-Akt和p-eNOS蛋白水平，抵消IH炎症继发的ROS增加。因此，S1P诱导的Akt/eNOS信号通路可能在保护IH诱导的ECs损伤中起重要作用。此外，S1P-MBs可能被设计为一种新型的S1P给药制剂，以在未来保护身体免受ECs损伤。
