年龄相关外周血单个核细胞线粒体功能与握力及四肢骨骼肌量的相关性

The correlation of age-related mitochondrial respiratory function of peripheral blood mononuclear cells with grip strength and appendicular skeletal muscle mass

目的研究人体外周血单个核细胞(PBMCs)的线粒体氧化呼吸能力与年龄相关的肌力、肌肉量下降的相关性,探讨老年人肌少症诊断的可能生物标志物。方法选取2019年6月至2020年8月江苏省人民医院老年内分泌科的住院患者65例,提取受试者PBMCs,借助组织细胞线粒体功能检测仪(Seahorse XF24,美国)进行线粒体呼吸功能的检测。使用手持式握力测力计测定握力,采用双能X线吸收骨密度仪测定四肢骨骼肌量(ASM),使用偏相关分析及多元线性回归模型进行多变量分析,评估年龄相关的外周血PBMCs的线粒体功能与握力及ASM的相关性。结果在校正性别及体质指数(BMI)后的偏相关分析结果显示,握力和ASM与年龄呈负相关(r=-0.537、-0.390,均P<0.001),PBMCs的线粒体基础呼吸、最大耗氧量、ATP的生成及呼吸储备与年龄也呈负相关(r=-0.558、-0.614、-0.526、-0.582,均P<0.001),握力和ASM均与线粒体的呼吸功能,包括基础呼吸、最大耗氧量、ATP生成、呼吸储备及质子漏呈明显正相关(握力:r=0.414、0.451、0.362、0.420、0.425,P=0.002、0.001、0.008、0.002、0.002;ASM:r=0.319、0.368、0.299、0.352、0.279,P=0.019、0.006、0.028、0.009、0.041)。进一步行多元线性回归分析结果显示,握力和ASM均与线粒体的呼吸功能,包括基础呼吸、最大耗氧量、ATP生成、呼吸储备及质子漏,呈正相关(握力:β=0.503、0.548、0.452、0.519、0.532,t=3.248、3.604、2.774、3.301、3.350,P=0.002、0.001、0.008、0.002、0.002;ASM:β=0.302、0.355、0.289、0.346、0.271,t=2.427、2.856、2.263、2.716、2.091,P=0.019、0.006、0.028、0.009、0.041)。年龄与PBMCs中线粒体基础呼吸、最大耗氧量、ATP生成及呼吸储备均呈负相关(β=-0.581、-0.654、-0.558、-0.640,t=-4.285、-5.157、-3.938、-4.863,均P<0.001),握力与ASM在回归分析中与PBMCs中线粒体基础呼吸、最大耗氧量、ATP生成及呼吸储备、质子漏均无明显相关(均P>0.05)。结论年龄相关PBMCs的线粒体氧化呼吸功能可反映肌力和肌肉量的变化,其与握力、ASM结合可作为评估老年人肌少症的新的生物标志物。

Objective To investigate the correlation of mitochondrial respiration function and oxidative phosphorylation of peripheral blood mononuclear cells(PBMCs)with grip strength and muscle mass in the elderly,and to identify potential biomarkers for the diagnosis of sarcopenia.Methods A total of 65 patients admitted to our hospital from June 2019 to August 2020 were enrolled in this study.PBMCs were extracted from subjects.Mitochondrial oxidative respiration function was assessed via the Seahorse XF24 analyzer.Grip strength was measured using a hydraulic dynamometer,and appendicular skeletal muscle mass(ASM)was estimated by dual-energy X-ray absorptiometry(DXA).Multivariate analysis was conducted by using partial correlation analysis and multiple linear regression,in order to evaluate the correlation of mitochondrial oxidative respiration function with grip strength and ASM.Results After adjustment for gender and body mass index(BMI),partial correlation analysis showed that grip strength and ASM had a negative correlation with age(r=-0.537 and-0.390,both P<0.001);and basal respiration,maximal respiration,ATP production and spare respiratory capacity of mitochondria in PBMCs were negatively correlated with age(r=-0.558,-0.614,-0.526 and-0.582,all P<0.001),whereas grip strength and ASM were positively correlated with basal respiration,maximal respiration,ATP production,spare respiratory capacity and proton leak of mitochondria in PBMCs(grip strength:r=0.414,0.451,0.362,0.420 and 0.425,P=0.002,0.001,0.008,0.002 and 0.002;ASM:r=0.319,0.368,0.299,0.352 and 0.279,P=0.019,0.006,0.028,0.009 and 0.041).Multiple linear regression analysis showed that grip strength and ASM were positively correlated with basal respiration,maximal respiration,ATP production,spare respiratory capacity and proton leak of mitochondria in PBMCs(grip:β=0.503,0.548,0.452,0.519 and 0.532,t=3.248,3.604,2.774,3.301 and 3.350,P=0.002,0.001,0.008,0.002 and 0.002;ASM:β=0.302,0.355,0.289,0.346 and 0.271,t=2.427,2.856,2.263,2.716 and 2.091,P=0.019,0.006,0.028,0.009 and 0.041).Age was negatively correlated with basal respiration,maximal respiration,ATP production and spare respiratory capacity of mitochondria in PBMCs(β=-0.581,-0.654,-0.558 and-0.640,t=-4.285,-5.157,-3.938 and-4.863,all P<0.001).Multiple linear regression analysis showed that ASM and grip strength had no significant correlation with basal respiration,maximal respiration,ATP production,spare respiratory capacity or proton leak of mitochondria in PBMCs.Conclusions Age-related mitochondrial oxidative respiration in PBMCs can reflect changes in muscle strength and muscle mass and,combined with grip strength and ASM,may be considered as a biomarker for the evaluation of sarcopenia in the elderly.