【摘要】 目的 探讨维持性血液透析(maintenance hemodialysis,MHD)患者外周血单核细胞(peripheral blood mononuclear cells,PBMC)中线粒体DNA(mitochondrial DNA,mtDNA)与Toll样受体9(toll like receptor 9,TLR9)/髓样分化因子88(myeloid differentiation factor 88,MyD88)/核因子κB(nuclear factor-κB,NF-κB)信号通路活化及肌肉减少症(sarcopenia,SP)的关系。方法 纳入2023年6月—2024年12月在浙江省仙居县人民医院行MHD治疗的患者，分为SP组及非肌肉减少症(nonsarcopenia,NSP)组。比较2组患者血生化指标，白细胞介素6(interleukin 6,IL-6)，肿瘤坏死因子α(tumor necrosis factor-α,TNF-α),PBMC中TLR9、MyD88、NF-κB、mtDNA，骨骼肌指数(skeletal muscle index,SMI)及握力的差异；分析SP发生的危险因素。结果 共纳入87例患者，其中SP组25例，NSP组62例。SP组IL-6(t=4.129,P<0.001)、TNF-α(t=4.483,P<0.001)、TLR9(t=5.207,P<0.001)、MyD88(t=7.918,P<0.001)、NF-κB(t=2.837,P=0.006)及mtDNA(t=2.081,P=0.040)表达均高于NSP组。mtDNA与TLR9、MyD88、NF-κB、IL-6及TNF-α呈正相关(r=0.338,P=0.001;r=0.415,P<0.001;r=0.451,P<0.001;r=0.569,P<0.001;r=0.435,P<0.001)。SMI及握力与TLR9、MyD88、NF-κB、IL-6、TNF-α、mtDNA均呈负相关(r=-0.490,P<0.001;r=-0.677,P<0.001;r=-0.421,P<0.001;r=-0.500,P<0.001;r=-0.388,P<0.001;r=-0.432,P<0.001及r=-0.400,P<0.001;r=-0.475,P<0.001;r=-0.323,P=0.002;r=-0.358,P=0.001;r=-0.274,P=0.010;r=-0.332,P=0.002)。MyD88(β=0.735,P<0.001)、TLR9(β=0.311,P<0.001)及mtDNA(β=0.185,P=0.008)水平升高是MHD患者发生SP的危险因素。结论 mtDNA可能通过活化TLR9/MyD88/NF-κB信号通路参与MHD患者SP的发生。更多还原

【Abstract】 Objective To investigate the relationship between mitochondrial DNA(mtDNA) in peripheral blood mononuclear cells(PBMC) and the activation of the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway, as well as its association with sarcopenia(SP) in patients undergoing maintenance hemodialysis(MHD). Methods Patients undergoing MHD treated at Zhejiang Xianju People’s Hospital from June 2023 to December 2024 were enrolled and divided into the SP group and the non-sarcopenia(NSP) group. The differences in biochemical blood indicators, interleukin 6(IL-6), tumor necrosis factor-α(TNF-α), TLR9, MyD88, NF-κB, mtDNA, skeletal muscle index(SMI), and handgrip strength were compared between the two groups. Risk factors for SP were analyzed. Results A total of 87 patients were enrolled, including 25 in the SP group and 62 in the NSP group. The levels of IL-6(t=4.129,P<0.001), TNF-α(t=4.483,P<0.001), TLR9(t=5.207,P<0.001), MyD88(t=7.918,P<0.001), NF-κB(t=2.837,P=0.006) and mtDNA(t=2.081,P=0.040) expression levels were all significantly higher in the SP group than in the NSP group. mtDNA was positively correlated with TLR9, MyD88,NF-κB, and TNF-α(r=0.338,P=0.001;r=0.415,P<0.001; r=0.451, P<0.001; r=0.569, P<0.001; r=0.435, P<0.001, respectively).SMI and handgrip strength were negatively correlated with TLR9, MyD88, NF-κB, IL-6, TNF-α, mtDNA(r=-0.490, P<0.001; r=-0.677, P<0.001; r=-0.421, P<0.001; r=-0.500,P<0.001; r=-0.388,P<0.001; r=-0.432, P<0.001 and r=-0.400, P<0.001;r=-0.475, P<0.001; r=-0.323, P=0.002; r=-0.358, P=0.001; r=-0.274, P=0.010; r=-0.332, P=0.002, respectively). Elevated levels of MyD88(β=0.735, P<0.001), TLR9(β=0.311, P<0.001) and mtDNA(β=0.185, P=0.008) were identified as risk factors for the development of SP in MHD patients. Conclusion mtDNA may contribute to the development of SP in MHD patients by activating the TLR9/MyD88/NF-κB signaling pathway.更多还原