同济大学学报（医学版）2025，Vol.46Issue(5)：669-676,8.DOI:10.12289/j.issn.2097-4345.25025
瑞马唑仑抑制前额叶皮质铁死亡缓解小鼠焦虑和抑郁样行为的研究
Remimazolam alleviates anxiety-and depression-like behaviors in mice by inhibiting ferroptosis in the prefrontal cortex
摘要
Abstract
Objective To explore the mechanism by which remimazolam alleviates anxiety-depressive symptoms by inhibiting ferroptosis.Methods An early life stress(ELS)mouse model was used,combined with maternal separation and restraint experiments,to simulate anxiety-depressive symptoms.The mice were treated with remimazolam,and behavioral experiments(sucrose preference test,open field test,elevated plus maze test,forced swim test,and tail suspension test)were conducted to assess anxiety-and depression-like behaviors.Serum analysis was performed to measure levels of depression-related factors,such as 5-hydroxytryptamine(5-HT),corticosterone(CORT),and brain-derived neurotrophic factor(BDNF).Additionally,immunohistochemistry and ferroptosis biochemical assays were used to evaluate the effect of remimazolam on ferroptosis in the prefrontal cortex.Furthermore,the ferroptosis inhibitory effect of remimazolam was verified in an Erastin-induced SH-SY5Y cell model.Result Remimazolam significantly alleviated anxiety-and depression-like behaviors in mice,as evidenced by improvements in the sucrose preference test,open field test,elevated plus maze test,forced swim test,and tail suspension test.Serum results indicated that remimazolam significantly reversed the changes in depression-related factors(5-HT,CORT,BDNF).Ferroptosis-related analysis showed that remimazolam increased the expression of GPX4 in the prefrontal cortex and significantly reduced the levels of MDA,GSH,and Fe2+,mitigating ferroptosis.In cell experiments,remimazolam inhibited Erastin-induced ferroptosis,significantly improved cell viability and reduced ROS and Fe2+levels.Conclusion It's demonstrated that remimazolam can alleviate anxiety-depressive symptoms by inhibiting ferroptosis.These findings provide a new research direction for the application of remimazolam in depression treatment.关键词
瑞马唑仑/铁死亡/焦虑/抑郁/早期生活压力Key words
remimazolam/ferroptosis/anxiety/depression/early life stress分类
医药卫生引用本文复制引用
罗青,张力文,郭家仪,施柳柳,赵文娟,杨泽勇..瑞马唑仑抑制前额叶皮质铁死亡缓解小鼠焦虑和抑郁样行为的研究[J].同济大学学报（医学版）,2025,46(5):669-676,8.基金项目
上海交通大学医工交叉重点项目(No:YG2022ZD029) （No:YG2022ZD029）
