数字中医药（英文）2025，Vol.8Issue(2)：267-278,12.DOI:10.1016/j.dcmed.2025.05.011
电针治疗骶上脊髓损伤后逼尿肌-膀胱颈协调障碍的蛋白质组学机制
Mechanism of electroacupuncture treating detrusor-bladder neck dyssynergia after suprasacral spinal cord injury by proteomics
摘要
Abstract
Objectives To elucidate the potential mechanisms of electroacupuncture(EA)in restoring detrusor-bladder neck dyssynergia(DBND)following suprasacral spinal cord injury(SSCI). Methods A total of 52 specific pathogen-free(SPF)grade famale Sprague-Dawley(SD)rats(10-12 weeks,250-280 g)were randomly assigned to either a sham group(n=12)or a spinal cord injury model group(n=40).In the model group,DBND was induced through Hassan Shaker spinal cord transection at T10 level,with 24 rats meeting inclusion criteria and subse-quently randomized into DBND group(n=12)and EA intervention group(DBND+EA group,n=12).After spinal shock recovery(day 19 after modeling),DBND+EA group received EA treatment at Ciliao(BL32),Zhongji(RN3),and Sanyinjiao(SP6)acupoints for 20 min per ses-sion at 10/50 Hz frequencies,once daily for 10 d.Sham and DBND groups received anesthe-sia only without EA intervention.On day 29 post-modeling,all rats underwent urodynamic assessments,followed by hematoxylin and eosin(HE)staining,tandem mass tag(TMT)pro-teomics,and Western blot(WB)analysis of detrusor and bladder neck tissues.Differentially expressed proteins(DEPs)were defined as proteins with P<0.05,unique peptides≥2,and fold change>1.2 or<0.83.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway anal-ysis was performed using KOBAS 3.0(P<0.01),and protein-protein interaction(PPI)net-works were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)11.5 and Cytoscape 3.9.1. Results Compared with sham group,DBND group showed significantly elevated leak point pressure(LPP)and maximum cystometric capacity(MCC)(both P<0.01).EA treatment sig-nificantly reduced both LPP and MCC compared with DBND group(P<0.01 and P<0.05,re-spectively).HE staining revealed that EA reduced detrusor fibrosis and improved bladder neck inflammation.TMT proteomics identified 30 overlapping DEPs in detrusor and 59 over-lapping DEPs in bladder neck when comparing DBND+EA/DBND groups with sham group.In detrusor tissue,KEGG analysis revealed 10 significantly enriched pathways(P<0.01),in-cluding mitogen-activated protein kinase(MAPK)signaling pathway.PPI analysis showed 22 of 30 DEPs were interconnected.In bladder neck tissue,14 pathways were significantly en-riched(P<0.01),including relaxin signaling pathway,with 51 of 59 DEPs showing intercon-nections.Both TMT and WB validations demonstrated that compared with sham controls,DBND rats exhibited upregulated collagen type IV alpha 2 chain(Col4a2)and downregulated guanine nucleotide-binding protein G(z)subunit alpha(Gnaz)in detrusor tissue,while EA treatment normalized both proteins(both P<0.05).In bladder neck tissue,DBND rats showed decreased expression of smoothelin(Smtn)and calcium-activated potassium chan-nel subunit beta-1(Kcnmb1)compared with sham controls(both P<0.01),which were both upregulated following EA treatment(P<0.01 and P<0.05,respectively). Conclusion EA restores detrusor-bladder neck coordination in DBND through dual-target mechanisms.In detrusor tissue,EA modulates contraction via extracellular matrix remodel-ing,cyclic adenosine monophosphate(cAMP)signaling pathway regulation,and enhanced adenosine triphosphate(ATP)biosynthesis mediated by neurotransmitters.In bladder neck tissue,EA promotes relaxation by maintaining contractile phenotypes,reducing fibrosis,sup-pressing smooth muscle excitation,and regulating presynaptic neurotransmitter release.These findings provide mechanistic insights into EA's therapeutic role in managing DBND.关键词
电针/骶上脊髓损伤/逼尿肌-膀胱颈协同失调/逼尿肌/膀胱颈/蛋白质组学分析/差异表达蛋白Key words
Electroacupuncture/Suprasacral spinal cord injury/Detrusor-bladder neck dyssynergia/Detrusor/Bladder neck/Proteomics analysis/Differentially expressed proteins引用本文复制引用
唐丽亚,瞿启睿,刘锦灿,许明,周璐,刘琼,艾坤..电针治疗骶上脊髓损伤后逼尿肌-膀胱颈协调障碍的蛋白质组学机制[J].数字中医药（英文）,2025,8(2):267-278,12.基金项目
National Natural Science Foundation of China(General Program,81874510),Natural Science Foundation of Hu-nan Province(2022JJ40301),and Scientific Research Project of the Hunan Provincial Department of Educa-tion(21B0369). （General Program,81874510）
