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首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >Longitudinal changes in total body creatine pool size and skeletal muscle mass using the D3‐creatine dilution method
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Longitudinal changes in total body creatine pool size and skeletal muscle mass using the D3‐creatine dilution method

机译：使用D3肌酸稀释法的总肌酸池大小和骨骼肌质量的纵向变化

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AbstractBackgroundWe recently validated in cross-sectional studies a new method to determine total body creatine pool size and skeletal muscle mass based on D3-creatine dilution from an oral dose and detection of urinary creatinine enrichment by isotope ratio mass spectrometry (IRMS). Routine clinical use of the method in aging and disease will require repeated application of the method, with a more widely available technology than IRMS, to enable determination of change in skeletal muscle mass in longitudinal studies. We therefore adapted the method to liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, and sought to establish proof of concept for the repeated application of the method in a longitudinal study. Because the turnover of creatine is slow, it was also critical to determine the impact of background enrichment from an initial dose of oral D3-creatine on subsequent, longitudinal measurements of change in muscle mass.MethodsRats were given an oral tracer dose of D3-creatine (1.0 mg/kg body weight) at 10 and 17 weeks of age. LC-MS/MS was used to determine urinary D3-creatine, and urinary D3-creatinine enrichment, at time intervals after D3-creatine administration. Total body creatine pool size was calculated from urinary D3-creatinine enrichment at isotopic steady state 72 h after administration of D3-creatine tracer.ResultsAt 10 weeks of age, rat lean body mass (LBM) measured by quantitative magnetic resonance correlated with creatine pool size (r = 0.92, P = 0.0002). Over the next 7 weeks, the decline in urinary D3-creatinine enrichment was slow and linear, with a rate constant of 2.73 ± 0.06 %/day. Subtracting background urinary D3-creatinine enrichment from the elevated enrichment following a second dose of D3-creatine at 17 weeks permitted repeat calculations of creatine pool size. As at 10 weeks, 17-week LBM correlated with creatine pool size (r = 0.98, P 0.0001). In addition, the change in creatine pool size was correlated with the change in LBM during the 7 weeks of rat growth between measurements (r = 0.96, P 0.0001).ConclusionThe LC-MS/MS-based D3-creatine dilution method can be applied repeatedly to measure total body creatine skeletal muscle mass change in longitudinal study.
机译：摘要背景我们最近在横断面研究中验证了一种基于口服剂量D 3 -肌酸稀释度确定总肌酸池大小和骨骼肌质量的新方法，并通过同位素比率质量检测尿肌酐富集情况光谱仪（IRMS）。该方法在衰老和疾病中的常规临床应用将要求该方法的重复应用，并且使用比IRMS更广泛的技术，以便能够在纵向研究中确定骨骼肌质量的变化。因此，我们使该方法适用于液相色谱-串联质谱分析（LC-MS / MS）技术，并寻求为在纵向研究中重复应用该方法建立概念验证。由于肌酸的代谢缓慢，因此从口服D 3 -肌酸的初始剂量确定背景富集对随后纵向测量肌肉质量变化的影响也至关重要。在10和17周龄时口服D 3 -肌酸示踪剂（1.0 mg / kg体重）。 LC-MS / MS用于在D 3 之后的时间间隔测定尿D 3 -肌酸和尿D 3 -肌酐的富集-肌酸给药。在施用D 3 -肌酸示踪剂后72小时，通过同位素稳态下尿D 3 -肌酐富集计算出了总的肌酸池大小。结果在10周龄时，大鼠通过定量磁共振测得的瘦体重（LBM）与肌酸池大小相关（r = 0.92，P = 0.0002）。在接下来的7周中，尿D 3 -肌酐富集的下降缓慢且呈线性，速率常数为2.73％±0.06％/天。在第17周第二次服用D 3 -肌酸后，从升高的富集中减去本底尿D 3 -肌酐的富集，可以重复计算肌酸池的大小。在10周时，17周的LBM与肌酸池大小相关（r = 0.98，P <0.0001）。此外，在两次测量之间的大鼠生长的7周期间，肌酸池大小的变化与LBM的变化相关（r = 0.96，P <0.0001）。结论基于LC-MS / MS的D 3 -creatine稀释法可重复用于测量全身肌酸骨骼肌质量变化。

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