氟化物诱导的内皮细胞代谢紊乱。

Fluoride induced metabolic disorder of endothelial cells.

机构信息

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, People's Republic of China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University, 23618504 Harbin, People's Republic of China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, People's Republic of China; Center for Chronic Disease Prevention and Control, Harbin Medical University, Harbin, People's Republic of China.

出版信息

Toxicology. 2023 Jun 15;492:153530. doi: 10.1016/j.tox.2023.153530. Epub 2023 Apr 28.

DOI:10.1016/j.tox.2023.153530

PMID:37121536

Abstract

Endemic fluorosis is a global public health problem. Cardiovascular diseases caused by fluoride are closely related to endothelial cell injury. Metabolism disorder of endothelial cells (ECs) are recognized as the key factor of endothelial dysfunction which has been a hot topic in recent years. However, the toxic effect of fluoride on vascular endothelium has not been elucidated. The aim of this study was to explore the alteration of endothelial cell metabolites in Human Umbilical Vein Endothelial Cells (HUVECs) exposed to NaF using LC-MS/MS technique. The screening conditions were Variable Importance for the Projection (VIP) > 1 and P < 0.05. It was found that the expression of the metabolites Lumichrome and S-Methyl-5'-thioadenosine was upregulated and of the other metabolites, such as Creatine, L-Glutamate, Stearic acid was downregulated. Differential metabolites were found to be primarily related to FoxO、PI3K/Akt and apoptosis signaling pathways by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. From the perspective of metabolism, this study explored the possible mechanism of fluoride induced endothelial cell injury which providing theories and clues for subsequent studies.

摘要

地方性氟中毒是一个全球性的公共卫生问题。氟引起的心血管疾病与内皮细胞损伤密切相关。内皮细胞（ECs）代谢紊乱被认为是内皮功能障碍的关键因素，这是近年来的一个热点问题。然而，氟对血管内皮的毒性作用尚未阐明。本研究旨在利用 LC-MS/MS 技术探讨 NaF 处理人脐静脉内皮细胞（HUVECs）后内皮细胞代谢物的变化。筛选条件为变量重要性投影（VIP）>1 和 P<0.05。结果发现，色氨酸吡咯啉酮和 S-甲基-5'-硫代腺苷的表达上调，而肌酸、L-谷氨酸、硬脂酸等其他代谢物的表达下调。差异代谢物通过京都基因与基因组百科全书（KEGG）富集分析主要与 FoxO、PI3K/Akt 和细胞凋亡信号通路相关。本研究从代谢角度探讨了氟化物诱导内皮细胞损伤的可能机制，为后续研究提供了理论和线索。