临床传统医学和药理学(英文)2025,Vol.6Issue(3):95-109,15.DOI:10.1016/j.ctmp.2025.200230
单细胞和全转录组RNA测序共同揭示电针抑制脊髓损伤后铁死亡的机制
Integrated single-cell and bulk RNA sequencing reveals the mechanisms of electroacupuncture in suppressing ferroptosis after spinal cord injury
摘要
Abstract
Background:Spinal cord injury causes severe disability,with ferroptosis,an iron-dependent cell death,con-tributing to its pathogenesis.Electroacupuncture is widely used in spinal cord injury treatment,but its effects on ferroptosis remain unclear. Objective:This study explores electroacupuncture's mechanisms on ferroptosis and its potential targets. Methods:Spinal cord injury was induced in rats at the T10 segment using a modified Allen's test.Electroacupunc-ture treatment was applied at Jiaji(EX-B2)acupoints with a 2/100 Hz frequency.Bulk and single-cell RNA se-quencing were used to analyze gene expression.Differential expression analysis was performed using DESeq2,and validations included qRT-PCR,western blot,immunohistochemistry,and lipid peroxidation assays. Results:Ferroptosis-related gene expression peaked on day 3 post-spinal cord injury.Electroacupuncture-treated rats showed improved motor function,reduced ferroptosis via Alox15 inhibition and GPX4 promotion,and de-creased neutrophil infiltration,evidenced by reduced myeloperoxidase expression.Single-cell RNA sequencing identified Fkbp5 as a key electroacupuncture target,predominantly expressed in oligodendrocytes.Cells with high Fkbp5 expression demonstrated lower ferroptosis scores and enhanced antioxidant capacity. Conclusion:Electroacupuncture reduces ferroptosis by mitigating reactive oxygen species production and neu-trophil infiltration.Fkbp5 may serve as a critical target for electroacupuncture,promoting antioxidant mechanisms in oligodendrocytes and providing new insights into spinal cord injury therapy.关键词
脊髓损伤/铁死亡/电针/全转录组测序/单细胞测序Key words
Spinal cord injury/Ferroptosis/Electroacupuncture/Bulk RNA-seq/scRNA-seq引用本文复制引用
张杰琪,黄怿,应熹晗,王若绮,张凯,吴磊,韩德雄,马睿杰,何克林..单细胞和全转录组RNA测序共同揭示电针抑制脊髓损伤后铁死亡的机制[J].临床传统医学和药理学(英文),2025,6(3):95-109,15.基金项目
This work was supported by the National Natural Science Foundation of China(grant 82205258 to K.L.H.,grant 82174487 to R.J.M.,grant 82205282 to L.W.) (grant 82205258 to K.L.H.,grant 82174487 to R.J.M.,grant 82205282 to L.W.)
Zhejiang Chinese Medical University Research Fund(grant 2022FSYYZZ08 to R.J.M.and D.X.H.,grant 2022FSYYZY09 to K.L.H.and R.J.M.). (grant 2022FSYYZZ08 to R.J.M.and D.X.H.,grant 2022FSYYZY09 to K.L.H.and R.J.M.)