血液透析患者血清成纤维细胞生长因子21与肌少症的关系及相关机制  

Relationship and associated mechanism of serum fibroblast growth factor 21 and sarcopenia in hemodialysis patients

作　　者：李旻[1] 张培 王彬 张梦雨 刘舒苏 CROMWELL NIKITA 杨敏[1] Li Min;Zhang Pei;Wang Bin;Zhang Mengyu;Liu Shusu;Nikita Cromwell;Yang Min(Department of Nephrology,the Third Affiliated Hospital of Soochow University,Changzhou 213003,China;Institute of Nephrology,Zhong Da Hospital,Southeast University School of Medicine,Nanjing 210009,China;Department of Nephrology,Georgetown Public Hospital Corporation,Georgetown,Guyana)

机构地区：[1]苏州大学附属第三医院肾内科,常州213003 [2]东南大学附属中大医院肾内科,南京210009 [3]Department of Nephrology,Georgetown Public Hospital Corporation,Georgetown,Guyana

出　　处：《中华肾脏病杂志》2023年第3期188-199,共12页Chinese Journal of Nephrology

基　　金：江苏省“333工程”培养资金资助项目(BRA2020156);常州市卫生健康青苗人才培养计划(CZQM2020028);常州市卫生健康委青年人才科技项目(QN201907);常州市科技支撑计划-社会发展项目(CE20215024)。

摘　　要：目的探讨血液透析(hemodialysis, HD)患者血清成纤维细胞生长因子21(fibroblast growth factor 21, FGF21)与肌少症的关系, 并在细胞水平初步探索尿毒症状态下FGF21与骨骼肌代谢相关信号通路的关系。方法该前瞻性观察性研究搜集2018—2019年苏州大学附属第三医院血液净化中心接受HD的患者资料。以ELISA法检测HD患者血清FGF21浓度, 同时根据第四胸椎(the fourth thoracic vertebra, T4)及第一腰椎(the first lumbar vertebra, L1)计算机断层扫描(computed tomography, CT)平面骨骼肌指数(skeletal muscle index, SMI)将患者分为肌少症组及非肌少症组, 分析FGF21与肌少症的关系。体外培养小鼠C2C12成肌细胞, 分别给予健康人血清、健康人血清+不同浓度FGF21、尿毒症血清、尿毒症血清+不同浓度FGF21干预细胞, 并采用Western印迹法检测各组肌肉环指蛋白-1(muscle ring finger protein-1, MURF1)、肌肉萎缩相关的F-box蛋白(muscle atrophy F-box, MAFbx/Atrogin-1)、成肌分化因子(myogenic differentiation, MyoD)、肌细胞生成素(myogenin, MyoG)的表达。结果共有118例HD患者被纳入此项研究, 其中男性64例(54.2%), 女性54例(45.8%), 年龄为(52.64±15.29)岁。118例HD患者有CT T4图像, 根据T4 SMI性别特异性最低四分位数(P25)为截点值分组(男性 < 59.92 cm^(2)/m^(2), 女性 < 46.75 cm^(2)/m^(2)), 肌少症组29例, 非肌少症组89例, 肌少症患者比例高达24.58%。82例患者有L1横断面图像, 根据L1 SMI性别特异性最低四分位数(P25)为截点值分组(男性 < 29.02 cm^(2)/m^(2), 女性 < 24.50 cm^(2)/m^(2)), 肌少症组20例, 非肌少症组62例, 肌少症患者比例高达24.39%。根据T4 SMI分组结果显示, 肌少症组患者血清FGF21水平高于非肌少症组, 但两组间差异无统计学意义[448.52(183.96, 1 684.08)ng/L比273.65(152.83, 535.54)ng/L, Z=-1.741, P=0.082]。根据L1 SMI分组结果显示, 肌少症组患者血清FGF21水平显著高于非肌少症组[460.95(188.91, 1Objective To investigate the relationship between serum fibroblast growth factor 21(FGF21)and sarcopenia in hemodialysis(HD)patients,and to explore the relationship between FGF21 and signal pathways related to skeletal muscle metabolism in uremic state at the cellular level.Methods The data of the HD patients from the blood purification center of the Third Affiliated Hospital of Soochow University were collected in this prospective observational study between January 2018 and December 2019.Serum FGF21 concentration was detected by enzyme-linked immunosorbent assay(ELISA).Meanwhile,the skeletal muscle indexes(SMI)at the fourth thoracic vertebra(T4)and the first lumbar vertebra(L1)were assessed by chest CT.According to the T4 SMI and L1 SMI,the patients were divided into sarcopenia group and non-sarcopenia group.The relationship between serum FGF21 and sarcopenia was analyzed.The C2C12 mouse myoblasts were cultured in vitro,which were intervened with healthy human serum,healthy human serum+different concentrations of FGF21,uremic serum,uremic serum+different concentrations of FGF21.The expressions of muscle ring finger protein-1(MURF1),muscle atrophy F-box(Atrogin-1),myogenic differentiation(MyoD)and myogenin(MyoG)were detected by Western blotting.Results A total of 118 HD patients with age of(52.64±15.29)years were enrolled in the study,including 64 males(54.2%)and 54 females(45.8%).The images at T4 and L1 level assessed by chest CT could be acquired from 118 patients and 82 patients,respectively.According to the lowest sex-specific quartile(P25)of T4 SMI(male<59.92 cm^(2)/m^(2),female<46.75 cm^(2)/m^(2))and the lowest sex-specific quartile(P25)of L1 SMI(male<29.02 cm^(2)/m^(2),female<24.50 cm^(2)/m^(2)),patients were divided into sarcopenia group and non-sarcopenia group,and there were 29(24.58%)and 20(24.39%)patients in the sarcopenia group,respectively.When the patients were divided into two groups according to the sex-specific lowest quartile of T4 SMI,although the serum FGF21 level in the sarcopenia group wa

关 键 词：肾透析 成纤维细胞生长因子 肌减少症 尿毒症 肌 骨骼 泛素蛋白酶体系统 

分 类 号：R692.5[医药卫生—泌尿科学] R685[医药卫生—外科学]