文献类型：期刊文献

英文题名：Empagliflozin Inhibits Neuronal Ferroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation by Activating the Nrf2/HO-1 Pathway

作者：Ma, Jialiang[1];Wang, Hongxia[2];Jia, Juan[1];Tao, Ting[1];Shan, Lingzhi[1];Sun, Shougang[1];Wang, Manxia[1]

第一作者：Ma, Jialiang

通信作者：Wang, MX[1]

机构：[1]Lanzhou Univ, Hosp 2, Lanzhou 730030, Peoples R China;[2]Gansu Univ Chinese Med, Lanzhou 730030, Peoples R China

第一机构：Lanzhou Univ, Hosp 2, Lanzhou 730030, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 2, Lanzhou 730030, Peoples R China.

年份：2025

外文期刊名：MOLECULAR NEUROBIOLOGY

收录：;Scopus(收录号：2-s2.0-86000287165);WOS:【SCI-EXPANDED(收录号:WOS:001437489000001)】；

基金：We thank all participants in this paper, especially the staff of Cuiying Biomedical Research Center of Lanzhou University Second Hospital

语种：英文

外文关键词：Empagliflozin; SGLT2i; Ferroptosis; OGD/R; Stroke; Ischemia-reperfusion injury

摘要：The impact of empagliflozin on OGD/R-induced ferroptosis in neurons is still unclear. This study aims to explore whether ferroptosis is associated with OGD/R-induced neuronal injury and the effect of empagliflozin on the ferroptosis effect of OGD/R-treated neurons. Western blotting, immunofluorescence, and RT-qPCR were used to detect the protein and mRNA levels of GPX4, Nrf2, and HO-1. ELISA, flow cytometry, and confocal microscopy were applied to analyze oxidative stress. Transmission electron microscopy and CCK-8 were used to determine the degree of ferroptosis in neurons. We observed a reduction in GPX4 levels and an increase in Nrf2 and HO-1 levels in OGD/R related neurons HT-22 cells. Notably, OGD/R elevates lipid peroxidation accumulation, ROS, Fe2+, and MDA levels while reducing GSH levels and decreasing mitochondrial membrane potential, leading to abnormal mitochondrial structure and eventual neuronal ferroptosis. Empagliflozin activates the Nrf2/HO-1 signaling pathway, enhances cellular antioxidant capacity, inhibits lipid peroxidation in OGD/R-treated neurons, and restores cellular iron homeostasis. In addition, empagliflozin can significantly reverse ferroptosis in OGD/R-treated neurons, and overexpression of Nrf2 combined with empagliflozin further inhibits ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be an essential cause of OGD/R-related neuron death. Empagliflozin exhibits a protective influence against OGD/R-induced ferroptosis by activating the Nrf2/HO-1 pathway.