基于代谢组学的儿童肥胖对青少年高血压发病风险的预测研究

Hypertension occurs in the early stage of life. It is of special importance and urgency to search for the high risk individual prediction and biological markers for early diagnosis of hypertension in children and adolescents. Obesity is a chronic disease with the highest incidence among children and adolescents, and is also an important risk factor for hypertension. Obesity is associated with significant metabolic changes in the body, but childhood obesity metabolic composition how to change, and its impact on adolescent hypertension has not been fully understood. Our previous study found that dietary characteristics were independent factors influencing hypertension, characteristic dietary intake had significant correlation with the changes of systolic blood pressure and diastolic blood pressure. It can’t be ignored that the effects of different dietary patterns on obesity metabolites. So we want to find features of metabolic end product, clear changes in the metabolic phenotype of obesity, and explore its effect on hypertension. We will use the method of metabonomics to analyze the metabolic mode of childhood obesity. Then we will use a prospective cohort study to investigate the metabolic patterns of childhood obesity in predicting the risk of hypertension. So it can provide the scientific basis for the early identification, intervention, and primary prevention of hypertension in child and adolescent hypertension susceptible people.

高血压源于生命早期，从儿童青少年时期寻找高血压高危个体预测和早期诊断的生物学标志对于高血压的一级预防有着特殊的重要性和迫切性。肥胖是儿童青少年中发病率最高的慢性病，也是高血压的重要危险因素。肥胖者体内伴随着明显的代谢改变，但儿童期肥胖代谢成分如何变化，及其对青少年高血压是否产生影响还没有被充分了解。我们前期研究发现饮食特征是高血压的独立影响因素，且特征性饮食的摄入量与收缩压和舒张压有显著性关联。而不同饮食结构对肥胖代谢产物的影响也是不可忽视的。我们据此提出假设，肥胖代谢模式对高血压的发生起到一定作用。我们将用代谢组学的方法，通过发现代谢产物的特征，明确儿童肥胖的代谢模式，并进一步用前瞻性队列研究方法，探讨这种代谢模式对高血压发病风险的预测，从而为儿童青少年高血压易感者的早期识别、干预，以及成人高血压的一级预防提供科学依据。

本项目旨在了解辽宁省肥胖儿童的基本状况，并应用代谢组学技术识别出儿童肥胖相关的代谢模式，建立了儿童肥胖代谢模式对高血压发病风险的预测模型。通过分层随机整群抽样，对辽宁省1885名中小学生开展了横断面调查，儿童肥胖率为15.54%，超重肥胖率为33.0%，超过全国平均水平。随机抽取了横断面调查样本中的105名研究对象，采用液相色谱-质谱联用技术（LC-MS）对肥胖、超重和正常体重三组儿童的血浆进行非靶向代谢组学分析，共定性出正负离子差异代谢物705种。用正交偏最小二乘-判别分析（OPLS-DA）对肥胖和正常体重儿童的血浆代谢物进行多变量分析，各组样本呈现明显的分离效果，表明肥胖和正常体重儿童的代谢物存在明显差异。利用KEGG平台对差异性代谢物进行代谢通路分析，我们发现肥胖和正常体重儿童血浆的差异代谢物主要集中在鞘脂类、嘌呤和嘧啶的代谢，苯丙胺酸、酪氨酸、色氨酸和类固醇激素的生物合成。因此，我们进一步在这些通路中进行肥胖、超重和正常体重三组间的比较，筛选出具有明显统计学差异且呈现出剂量反应关系的重要代谢物5种，分别为莽草酸，左旋色氨酸，胸苷，13-顺式视黄醇和氨基甲酰磷酸。根据儿童肥胖的重要差异代谢物，绘制ROC曲线，发现4-羟基雌二醇和PC 38:6两种代谢物对儿童高血压的发生具有一定预测作用，可以为高血压的一级预防提供一定基础。