4~6岁阻塞性睡眠呼吸暂停低通气综合征患儿肠道代谢产物特征及临床价值分析

doi:10.7499/j.issn.1008-8830.2309129

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摘要目的探究4~6岁阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apnea-hypopnea syndrome, OSAHS）患儿肠道代谢产物特征及其临床价值。方法前瞻性纳入31例4~6岁OSAHS患儿作为试验组，24例4~6岁健康儿童作为对照组，记录相关临床指标。收集粪便标本，通过液-质联用非靶向代谢组学检测所有代谢产物。结果共检测出206种代谢产物，主要为氨基酸及其衍生物。试验组儿童肠道代谢产物整体构成与对照组差异有统计学意义（P<0.05）。共筛选出18种差异代谢产物，6种代谢产物（N-乙酰蛋氨酸、L-蛋氨酸、L-赖氨酸、DL-苯丙氨酸、L-酪氨酸和L-异亮氨酸）用于诊断OSAHS的受试者操作特征曲线下面积大于0.7。其中N-乙酰蛋氨酸曲线下面积最大，为0.807，灵敏度为70.83%，特异度为80.65%。差异代谢产物与临床指标相关性分析显示，扁桃体肿大程度与肠内酯，尿酸与苯乙醛，血糖与N-乙酰蛋氨酸，胆固醇与9-六溴二苯醚和普鲁卡因呈正相关（P<0.05）；扁桃体肿大程度与N-甲基酪胺，AST与吲哚丙烯酸和L-异亮氨酸，ALT与DL-苯丙氨酸、吲哚丙烯酸和L-异亮氨酸，尿酸与羟喹啉，尿素氮与N,N-二环己脲呈负相关（P<0.05）。差异代谢产物影响的代谢功能通路主要有核黄素代谢、精氨酸和脯氨酸代谢、泛酸和辅酶A生物合成、半胱氨酸和蛋氨酸代谢、赖氨酸降解和谷胱甘肽代谢等。结论 4~6岁OSAHS患儿肠道代谢产物与代谢功能发生改变，主要为氨基酸代谢紊乱，筛选出的肠道差异代谢产物作为OSAHS生物标志物具有潜在的筛查诊断价值。

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关键词 ：阻塞性睡眠呼吸暂停低通气综合征, 肠道代谢产物, 生物标志物, 代谢功能, 儿童

Abstract：Objective To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods A total of 31 children aged 4-6 years with OSAHS were prospectively enrolled as the test group, and 24 healthy children aged 4-6 years were included as the control group. Relevant clinical indicators were recorded. Fecal samples were collected, and non-targeted metabolomics analysis using liquid chromatography-mass spectrometry was performed to detect all metabolites. Results A total of 206 metabolites were detected, mainly amino acids and their derivatives. There was a significant difference in the overall composition of intestinal metabolites between the test and control groups (P<0.05). Eighteen different metabolites were selected, among which six (N-acetylmethionine, L-methionine, L-lysine, DL-phenylalanine, L-tyrosine, and L-isoleucine) had receiver operating characteristic curve areas greater than 0.7 for diagnosing OSAHS. Among them, N-acetylmethionine had the largest area under the curve, which was 0.807, with a sensitivity of 70.83% and a specificity of 80.65%. Correlation analysis between different metabolites and clinical indicators showed that there were positive correlations between the degree of tonsil enlargement and enterolactone, between uric acid and phenylacetaldehyde, between blood glucose and acetylmethionine, and between cholesterol and 9-bromodiphenyl and procaine (P<0.05). There were negative correlations between the degree of tonsil enlargement and N-methyltyramine, aspartate aminotransferase and indolepropionic acid and L-isoleucine, between alanine aminotransferase and DL-phenylalanine, between indolepropionic acid and L-isoleucine, between uric acid and hydroxyquinoline, and between urea nitrogen and N,N-dicyclohexylurea (P<0.05). The metabolic functional pathways affected by differential metabolites mainly included riboflavin metabolism, arginine and proline metabolism, pantothenic acid and coenzyme A biosynthesis, cysteine and methionine metabolism, lysine degradation and glutathione metabolism. Conclusions Intestinal metabolites and metabolic functions are altered in children aged 4-6 years with OSAHS, primarily involving amino acid metabolism disorders. The screened differential intestinal metabolites have potential screening and diagnostic value as biomarkers for OSAHS.

Key words： Obstructive sleep apnea-hypopnea syndrome Intestinal metabolite Biomarker Metabolic function Child

收稿日期: 2023-09-25

基金资助:浙江省医药卫生科技计划（2024KY1576）；第一批宁波市临床医学研究中心依托单位（2019A21002）；宁波市社会公益研究项目（2021S100）；宁波市医学重点学科建设计划（2022-B17）；宁波市医疗卫生高端团队项目（2022020405）。

通讯作者: 邱海燕，女，主任医师。Email：nbfeqhy@163.com。 E-mail: nbfeqhy@163.com

作者简介: 陈悦，女，硕士研究生；

引用本文:

陈悦,卢燕波,吴军华等. 4~6岁阻塞性睡眠呼吸暂停低通气综合征患儿肠道代谢产物特征及临床价值分析[J]. 中国当代儿科杂志, 2024, 26(6): 575-583.

CHEN Yue,LU Yan-Bo,WU Jun-Hua et al. Characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome[J]. CJCP, 2024, 26(6): 575-583.

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