南方医科大学学报2024，Vol.44Issue(8)：1441-1449,9.DOI:10.12122/j.issn.1673-4254.2024.08.02
开心散通过减轻前额叶皮质铁死亡缓解小鼠的阿霉素化疗性抑郁
Kaixinsan alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex
摘要
Abstract
Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.关键词
开心散/乳腺癌/化疗/抑郁/铁死亡Key words
Kaixinsan/breast cancer/chemotherapy/depression/ferroptosis引用本文复制引用
欧阳明子,崔佳琦,王慧,梁正,皮大锦,陈利国,陈前军,吴迎朝..开心散通过减轻前额叶皮质铁死亡缓解小鼠的阿霉素化疗性抑郁[J].南方医科大学学报,2024,44(8):1441-1449,9.基金项目
国家自然科学基金(81873155,81974571,82274513,82305234) （81873155,81974571,82274513,82305234）
广东省自然科学基金(2020A15110760,2023A1515011115) （2020A15110760,2023A1515011115）
广州市科技计划(SL2023A03J01120,SL2023A04J00228) （SL2023A03J01120,SL2023A04J00228）
广东省中医院中医药科技专项科研项目(YN2022QN32) （YN2022QN32）
广东省中医证候临床研究重点实验室项目(YN2023ZH10) （YN2023ZH10）
中医湿证国家重点实验室自主项目(QZ2023ZZ13) （QZ2023ZZ13）
第七批全国老中医药专家学术经验继承工作Supported by National Natural Science Foundation of China(81873155,81974571,82274513,82305234). （81873155,81974571,82274513,82305234）
