Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury  

作　　者：Yu Kang Rui Zhu Shuang Li Kun-Peng Qin Hao Tang Wen-Shan Shan Zong-Sheng Yin 

机构地区：[1]Department of Orthopedics,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui Province,China

出　　处：《Neural Regeneration Research》2023年第4期881-888,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81871785 and 81672161(both to ZSY)。

摘　　要：Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.

关 键 词：ERYTHROPOIETIN ferroptosis Gpx4 iron overload lipid peroxidation mechanism neurological function recovery spinal cord injury spinal neuron xCT 

分 类 号：R651.2[医药卫生—外科学]