We previously identified the urinary biomarkers to diagnose calcium deficiency and nutritional rickets by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS). To find biomarkers of calcium deficiency and further confirm these biomarkers in serum, we performed serum metabolomics analysis of calcium-deficient rats. A calcium-deficient rat model was established with a low-calcium diet for 12 weeks. Serum metabolomics based UPLC/Q-TOF MS/MS and multivariate statistical analysis was performed to identify the alterations in metabolites associated with calcium deficiency in rats. Bone mineral density, serum parathyroid hormone and alkaline phosphatase were significantly decreased in the low-calcium diet group (LCG) compared to the normal calcium diet group (NCG). Serum metabolic-profiling analysis could definitively distinguish between the LCG and NCG and identified 24 calcium-deficient biomarkers. Three metabolites (indoxyl sulfate, phosphate, and taurine) of the 24 biomarkers were found in our previous urinary metabolomics study of rats with a calcium deficiency and nutritional rickets. The areas under the curve (AUCs) of these three biomarkers were greater than 0.8, and the combination of any two biomarkers was higher than 0.95. Dietary calcium deficiency induced the alterations of metabolites in the serum of rats, and the three identified biomarkers had relatively high diagnostic values for calcium deficiency in rats.

中文翻译：

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基于UPLC / Q-TOF MS / MS的代谢组学鉴定的缺钙大鼠血清生物标志物

我们之前通过超高效液相色谱/四极杆飞行时间串联质谱（UPLC / Q-TOF MS / MS）鉴定了尿液生物标志物，以诊断钙缺乏症和营养性病。为了找到缺钙的生物标志物并进一步确认血清中的这些生物标志物，我们对缺钙的大鼠进行了血清代谢组学分析。建立低钙饮食12周的缺钙大鼠模型。进行了基于UPLC / Q-TOF MS / MS的血清代谢组学和多变量统计分析，以鉴定与大鼠缺钙相关的代谢产物的变化。与正常钙饮食组（NCG）相比，低钙饮食组（LCG）的骨矿物质密度，血清甲状旁腺激素和碱性磷酸酶显着降低。血清代谢谱分析可以明确地区分LCG和NCG，并鉴定出24种钙缺乏生物标志物。在我们先前对钙缺乏和营养性病的大鼠进行的尿代谢组学研究中，发现了24种生物标记物中的3种代谢物（硫酸吲哚酚，磷酸盐和牛磺酸）。这三个生物标志物的曲线下面积（AUC）大于0.8，并且任意两个生物标志物的组合均大于0.95。饮食中钙的缺乏会引起大鼠血清代谢产物的改变，并且三种已鉴定的生物标志物对大鼠的钙缺乏具有较高的诊断价值。和牛磺酸）中的24种生物标记物是在我们先前对钙缺乏和营养性rick病的大鼠进行的尿代谢组学研究中发现的。这三个生物标志物的曲线下面积（AUC）大于0.8，并且任意两个生物标志物的组合均大于0.95。饮食中钙的缺乏会引起大鼠血清代谢产物的改变，并且三种已鉴定的生物标志物对大鼠的钙缺乏具有较高的诊断价值。和牛磺酸）中的24种生物标记物是在我们先前对钙缺乏和营养性rick病的大鼠进行的尿代谢组学研究中发现的。这三个生物标志物的曲线下面积（AUC）大于0.8，并且任意两个生物标志物的组合均大于0.95。饮食中钙缺乏引起大鼠血清中代谢产物的变化，并且三种已鉴定的生物标志物对大鼠钙缺乏具有较高的诊断价值。