学龄期肥胖儿童尿液中小分子代谢物研究

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摘要目的采用气相色谱-质谱联用（GC/MS）代谢组学技术分析学龄期肥胖儿童尿液中小分子代谢物的变化，筛选出与学龄期儿童肥胖相关的尿液中差异代谢物，探讨学龄期肥胖儿童代谢紊乱的发生机制。方法 2018年3月至12月，对上海市宝山区中西医结合医院卫生保健科中体检的学校名单采用随机数字表进行编号，从中随机选取上海市宝山区实验小学、上海大学附属实验学校及宝山共富实验学校3所学校12～15岁儿童的体检资料，并从中筛选出12～15岁的25名肥胖儿童作为肥胖组，同时选取一组年龄、性别匹配的25名正常儿童作为正常组。采用GC/MS检测两组尿液中小分子代谢物，运用多维统计方法-偏最小二乘法判别分析（PLS-DA）观察两组样本的尿液代谢谱，依据权重系数VIP＞1，P ＜ 0.05，获得差异性代谢物，利用商业化的代谢物谱库（NIST、Wiley Registry）鉴定差异代谢物。结果与正常组比较，肥胖组身高、体重、体重指数、甘油三酯、谷丙转氨酶、低密度脂蛋白均显著升高，差异有统计学意义（P ＜ 0.05或P ＜ 0.01），高密度脂蛋白显著降低，差异有高度统计学意义（P ＜ 0.01）。肥胖组和正常组的代谢谱分离良好，鉴定了38个差异代谢物，缬氨酸、异亮氨酸、酪氨酸等18个尿液中的代谢物受试者工作特征曲线的曲线下面积＞0.5，学龄期肥胖儿童患者体内存在苯丙氨酸、酪氨酸和色氨酸的生物合成，苯丙氨酸代谢，甘油脂代谢，酪氨酸代谢和组氨酸代谢等代谢异常。结论缬氨酸、异亮氨酸、酪氨酸、尿酸等18个尿液中的特征代谢物有望成为诊断学龄期肥胖儿童潜在的生物标志物。采用代谢组学方法筛选的学龄期肥胖儿童尿液中的差异性代谢产物，为临床学龄期儿童肥胖的诊断和治疗提供一定的实验基础。

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	张艳涛1 陈黎1 朱一冰1 王淑玲2 苟小军1

关键词 ：代谢组学, 学龄期, 肥胖儿童, 尿液, 生物标志物

Abstract：Objective To analyze the changes of small molecular metabolites in urine of school-age children with obesity by gas chromatography-mass spectrometry (GC/MS) metabolomics technology, and screen out the differential metabolites in urine related to obesity in school-age children, so as to explore the occurrence mechanism of metabolic disorders in school-age children with obesity. Methods From March to December 2018, the list of physical examination schools in Department of Health Care, Baoshan District Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Shanghai was numbered by random number table, and the physical examination data of children aged 12 to 15 in Baoshan Experimental Primary School, Shanghai University Affiliated Experimental School and Baoshan Gongfu Experimental School of Shanghai were randomly selected. Twenty-five obese children aged 12-15 were selected as the obese group, and a group of 25 normal children matched with age and sex were selected as the normal group. GC/MS was used to detect small molecular metabolites in urine of the two groups, and multidimensional statistical method-partial least squares-discriiminate (PLS-DA) was used to observe the urine metabolism profile of the two groups. According to the weight coefficient VIP>1, P ＜ 0.05, the differential metabolites were obtained. Differential metabolites were identified using commercial metabolite profiles (NIST and Wiley Registry). Results Compared with normal group, height, body weight, body mass index, triglyceride, alanine aminotransferase, and low density lipoprotein were significantly increased in obese group, and the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01), while high density lipoprotein was significantly decreased, and the difference was highly statistically significant (P ＜ 0.01). The metabolic profiles of the obese group and the normal group were well separated and 38 different metabolites were identified. The area under the curve of receiver operating characteristic curve of 18 metabolites in urine, such as valine, isoleucine, and tyrosine, was > 0.5. School-age children with obesity have metabolic abnormalities such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerol metabolism, tyrosine metabolism and histidine metabolism. Conclusion Eighteen characteristic metabolites in urine such as valine, isoleucine, tyrosine and uric acid are expected to be potential biomarkers in the diagnosis of school-age children with obesity. Differential metabolites in urine of school-age children with obesity are screened by metabonomics method, which provide a certain experimental basis for the diagnosis and treatment of obesity in school-age children.

Key words： Metabolomics School age Obese children Urine Biomarker

基金资助:国家自然科学基金面上项目（82074052）；
上海市卫生和计划生育委员会科研课题（20154Y0148）；
浙江省杭州市农业与社会发展科研自主申报项目（20191203B17）。

通讯作者: 苟小军（1975.3-），男，博士，主任药师；研究方向：临床药学与代谢研究。

作者简介: 张艳涛（1982.10-），女，硕士；研究方向：儿科内分泌临床研究。

引用本文:

张艳涛1 陈黎1 朱一冰1 王淑玲2 苟小军1. 学龄期肥胖儿童尿液中小分子代谢物研究[J]. 中国医药导报, 2022, 19(11): 4-10,15.
ZHANG Yantao1 CHEN Li1 ZHU Yibing1 WANG Shuling2 GOU Xiaojun1. Study on small molecular metabolites in urine of school-age children with obesity#br#. 中国医药导报, 2022, 19(11): 4-10,15.

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https://www.yiyaodaobao.com.cn/CN/ 或 https://www.yiyaodaobao.com.cn/CN/Y2022/V19/I11/4

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