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...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.展开更多
目的探讨骶神经调控(SNM)对神经源性膀胱(NB)患者储尿期尿动力学参数的影响,为客观评价SNM的疗效提供更全面的参考依据。方法回顾性分析2012年10月—2025年5月于中国康复研究中心北京博爱医院接受SNM治疗的49例NB患者的临床资料。收集...目的探讨骶神经调控(SNM)对神经源性膀胱(NB)患者储尿期尿动力学参数的影响,为客观评价SNM的疗效提供更全面的参考依据。方法回顾性分析2012年10月—2025年5月于中国康复研究中心北京博爱医院接受SNM治疗的49例NB患者的临床资料。收集患者的基线资料、影像尿动力学参数,评估患者一期测试前后的膀胱最大测压容量、充盈期最大逼尿肌压力及膀胱顺应性变化,并分析逼尿肌过度活动(DO)、膀胱输尿管反流(VUR)的改善情况。结果49例患者中男性27例,女性22例,平均年龄(37.41±15.15)岁,中位病程为5.0(2.0,15.5)年,中位随访时间为11(1,32)个月。有37例(75.5%)接受永久性骶神经刺激器植入术(永久性植入组),其余12例归入非永久性植入组。一期测试前后,全部患者的膀胱最大测压容量显著增加[218.0(93.0,358.5)mL vs.300.0(238.5,400.0)mL,P<0.001],充盈期最大逼尿肌压力降低[32.0(13.5,71.0)cmH_(2) O vs.20.0(9.0,50.0)cmH_(2) O,P<0.001],膀胱顺应性提高[11.8(8.3,25.6)mL/cmH_(2) O vs.26.7(8.6,44.1)mL/cmH_(2) O,P<0.001]。永久性植入组患者一期测试前后的膀胱最大测压容量增加[(239.16±147.23)mL vs.(312.24±121.83)mL,P<0.001],充盈期最大逼尿肌压力降低[32.0(15.0,58.0)cmH_(2) O vs.15.0(9.0,41.0)cmH_(2) O,P<0.05],膀胱顺应性改善[10.8(8.3,23.6)mL/cmH_(2) O vs.28.6(8.6,41.4)mL/cmH_(2) O,P<0.001]。非永久性植入组患者一期测试前后膀胱最大测压容量、充盈期最大逼尿肌压力、膀胱顺应性比较,差异均无统计学意义(P>0.05)。永久性植入组患者中有17例患者接受了影像尿动力学随访,与测试前比较,该组患者测试后及截至随访时的充盈期最大逼尿肌压力、膀胱顺应性均有明显改善(P<0.05);但该组患者测试后与截至随访时的膀胱最 大测压容量、充盈期最大逼尿肌压力、膀胱顺应性比较,差异无统计学意义(P>0.05)。49例患者中存在DO患者21例,VUR患者20例,测试后以及截至随访时患者的DO与VUR均有改善。结论本研究通过储尿期尿动力学参数客观评估证实SNM可有效改善NB患者的储尿功能,改善DO和膀胱顺应性,并使部分患者VUR消失或减轻,长期随访证实SNM疗效稳定。展开更多
膀胱ICC细胞(Interstitial cells of Cajal in bladder)早在上个世纪已被发现,与胃肠道ICC细胞同族,膀胱ICC以自发电活动为特性,源于胞内贮存钙离子释放和钙激活的氯同道开放引起自发短暂去极化。膀胱ICC细胞起初被理解为起搏细胞,其自...膀胱ICC细胞(Interstitial cells of Cajal in bladder)早在上个世纪已被发现,与胃肠道ICC细胞同族,膀胱ICC以自发电活动为特性,源于胞内贮存钙离子释放和钙激活的氯同道开放引起自发短暂去极化。膀胱ICC细胞起初被理解为起搏细胞,其自发的电活动作为起搏器引起下游平滑肌的收缩,这种假说尚缺乏立足的直接证据,目前认为ICC细胞仅仅是膀胱平滑肌收缩活动的调节器,与上皮-传入神经以及神经-平滑肌的信号传递密切相关。病理状态下ICC细胞的作用似乎比生理状态下更为突出,例如膀胱过度活动症,多篇文献报道膀胱过度活动症患者膀胱的ICC细胞数目比正常增多,而且其平滑肌的收缩对酪氨酸激酶受体(tyrosine kinase receptor,c-Kit)拮抗剂格列卫更加敏感。未来膀胱ICC细胞的研究集中在阐明病理及生理状态下ICC的作用机制和信号通路。展开更多
基金National Natural Science Foundation of China (General Program, 81874510)Natural Science Foundation of Hunan Province (2022JJ40301)Scientific Research Project of the Hunan Provincial Department of Education (21B0369)。
文摘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.
文摘目的探讨骶神经调控(SNM)对神经源性膀胱(NB)患者储尿期尿动力学参数的影响,为客观评价SNM的疗效提供更全面的参考依据。方法回顾性分析2012年10月—2025年5月于中国康复研究中心北京博爱医院接受SNM治疗的49例NB患者的临床资料。收集患者的基线资料、影像尿动力学参数,评估患者一期测试前后的膀胱最大测压容量、充盈期最大逼尿肌压力及膀胱顺应性变化,并分析逼尿肌过度活动(DO)、膀胱输尿管反流(VUR)的改善情况。结果49例患者中男性27例,女性22例,平均年龄(37.41±15.15)岁,中位病程为5.0(2.0,15.5)年,中位随访时间为11(1,32)个月。有37例(75.5%)接受永久性骶神经刺激器植入术(永久性植入组),其余12例归入非永久性植入组。一期测试前后,全部患者的膀胱最大测压容量显著增加[218.0(93.0,358.5)mL vs.300.0(238.5,400.0)mL,P<0.001],充盈期最大逼尿肌压力降低[32.0(13.5,71.0)cmH_(2) O vs.20.0(9.0,50.0)cmH_(2) O,P<0.001],膀胱顺应性提高[11.8(8.3,25.6)mL/cmH_(2) O vs.26.7(8.6,44.1)mL/cmH_(2) O,P<0.001]。永久性植入组患者一期测试前后的膀胱最大测压容量增加[(239.16±147.23)mL vs.(312.24±121.83)mL,P<0.001],充盈期最大逼尿肌压力降低[32.0(15.0,58.0)cmH_(2) O vs.15.0(9.0,41.0)cmH_(2) O,P<0.05],膀胱顺应性改善[10.8(8.3,23.6)mL/cmH_(2) O vs.28.6(8.6,41.4)mL/cmH_(2) O,P<0.001]。非永久性植入组患者一期测试前后膀胱最大测压容量、充盈期最大逼尿肌压力、膀胱顺应性比较,差异均无统计学意义(P>0.05)。永久性植入组患者中有17例患者接受了影像尿动力学随访,与测试前比较,该组患者测试后及截至随访时的充盈期最大逼尿肌压力、膀胱顺应性均有明显改善(P<0.05);但该组患者测试后与截至随访时的膀胱最 大测压容量、充盈期最大逼尿肌压力、膀胱顺应性比较,差异无统计学意义(P>0.05)。49例患者中存在DO患者21例,VUR患者20例,测试后以及截至随访时患者的DO与VUR均有改善。结论本研究通过储尿期尿动力学参数客观评估证实SNM可有效改善NB患者的储尿功能,改善DO和膀胱顺应性,并使部分患者VUR消失或减轻,长期随访证实SNM疗效稳定。
文摘膀胱ICC细胞(Interstitial cells of Cajal in bladder)早在上个世纪已被发现,与胃肠道ICC细胞同族,膀胱ICC以自发电活动为特性,源于胞内贮存钙离子释放和钙激活的氯同道开放引起自发短暂去极化。膀胱ICC细胞起初被理解为起搏细胞,其自发的电活动作为起搏器引起下游平滑肌的收缩,这种假说尚缺乏立足的直接证据,目前认为ICC细胞仅仅是膀胱平滑肌收缩活动的调节器,与上皮-传入神经以及神经-平滑肌的信号传递密切相关。病理状态下ICC细胞的作用似乎比生理状态下更为突出,例如膀胱过度活动症,多篇文献报道膀胱过度活动症患者膀胱的ICC细胞数目比正常增多,而且其平滑肌的收缩对酪氨酸激酶受体(tyrosine kinase receptor,c-Kit)拮抗剂格列卫更加敏感。未来膀胱ICC细胞的研究集中在阐明病理及生理状态下ICC的作用机制和信号通路。
