Effect of Mild Hypothermia on the Related Factors of Nrf2-Keap1-ARE Signaling Pathway in Neonates with Hypoxic-Ischemic Encephalopathy

Wang Zhansheng; Wang Pin; Liu Yulu

doi:10.3969/j.issn.1004-5775.2025.18.001

Abstract：Objective:To study the effects of mild hypothermia on the Nrf2-Keap1-ARE signaling pathway related factors in neonates with hypoxic-ischemic encephalopathy(NHIE).Methods:A total of 83 children with NHIE diagnosed in the hospital from January 2021 to December 2023 were divided into two groups according to the examination results and treatment modes.The control group(41 cases)received routine treatment such as sedation and oxygen inhalation.The study group(42 cases)was treated with mild hypothermia on the basis of routine treatment.The clinical efficacy,recovery time of clinical symptoms,brain injury markers[vertebral protein-like protein 1(VILIP-1),neuron-specific enolaseb(NSE),S100β protein],oxidative stress indicators[superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA)]and nuclear factor E2 related factor(NRF)were compared between the two groups.Results:The total clinical effective rate of the study group was higher than the control group,and the difference was statistically significant(χ2=4.672,P＜0.05).The recovery time of each clinical symptom in the study group was shorter than the control group,and the differences were statistically significant(t=7.998,3.686,5.720,7.949;P＜0.001).After treatment,the MDA content in the study group was lower than the control group,while the SOD and GSH-Px contents were higher than the control group,and the differences were statistically significant(t=3.760,6.640,4.393;P＜0.001).After treatment,the expression level of Nrf2 and ARE mRNA in the study group were higher than the control group,while the expression level of Keap1 mRNA was lower than the control group,and the differences were all statistically significant(t=7.760,7.129,4.783;P＜0.001).After treatment,the contents of VILIP-1,NSE and S100β in the study group were lower than the control group,and the differences were statistically significant(t=3.987,3.862,3.685;P＜0.001).Conclusion:Mild hypothermia treatment of NHIE can effectively inhibit oxidative stress response,alleviate brain damage,and regulate the expression of key factors in the Nrf2-Keap1-ARE signaling pathway.