Chinese Journal of Blood Purification

Chinese Journal of Blood Purification ›› 2025, Vol. 24 ›› Issue (12): 999-103.doi: 10.3969/j.issn.1671-4091.2025.12.007

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Study on the role of mitochondrial DNA in the pathogenesis of sarcopenia in maintenance hemodialysis patients via activation of the Toll-like receptor 9/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway

QIU Jie-shan,FANG Shen-shen,JI Li-jun,XU Zhi-yong,DING Yan,ZHOU Shu-lan,ZHANG Ting-yu   

  1. Department of Nephrology, Xianju People’s Hospital, Southeast district of Zhejiang Provincial People's Hospital, Xianju 317300, China
  • Received:2025-04-08 Revised:2025-07-14 Online:2025-12-12 Published:2025-12-12
  • Contact: 317300 台州，仙居县人民医院浙江省人民医院浙东南院区1肾脏内科 E-mail:qiujieshanww@126.com

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.

Key words: Mitochondrial DNA, Myeloid differentiation factor 88, Nuclear factor-κB, Maintenance hemodialysis, Sarcopenia

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