清晨型与夜晚型量表得分对中国年轻人尿邻苯二甲酸酯代谢物与炎症细胞因子关联的调节作用：一项人体生物监测研究

Moderating effects of reduced Morning and Evening Questionnaire scores on the association between urinary phthalate metabolites and inflammatory cytokines among Chinese young adults: a human biomonitoring study

清晨型与夜晚型量表得分对中国年轻人尿邻苯二甲酸酯代谢物与炎症细胞因子关联的调节作用：一项人体生物监测研究

Authors: Tingting Li, Shuman Tao, Tangjun Jiang, Wanyu Che, Liwei Zou, Yajuan Yang, Fangbiao Tao, Xiaoyan Wu

Source：Environmental Toxicology And Pharmacology

PMID: 40543636

DOI: 10.1016/j.etap.2025.104749 

Abstract

Although previous findings have suggested that phthalate exposure was related to inflammation in young adults, little is known about whether chronotype, measured by the reduced Morning and Evening Questionnaire (rMEQ), reflects a moderating or mediating effect of phthalate exposure on inflammation. To address these gaps, this study examined the correlation of phthalate metabolites with inflammatory cytokines in Chinese young adults and explored the moderating effects of rMEQ scores in this association. From April to May 2019, 1,179 young adults were recruited from 2 universities in Hefei and Shangrao cities. Among them, 1,135 completed valid self-administered questionnaires, 1,012 provided sufficient urine samples for phthalate metabolites analysis, and 744 provided fasting blood samples for the determination of inflammatory cytokines levels. The high-performance liquid chromatography-tandem mass spectrometry was adopted to determine the concentration of urinary phthalate metabolites. A liquid-phase protein suspension chip detection instrument was utilized to detect the levels of inflammatory cytokines in the supernatant. The rMEQ was adopted as a measure of chronotype. The generalized linear model was established to determine the association of phthalate metabolites with inflammatory cytokines. Moderating analysis was used to examine whether rMEQ scores moderated the relationships of phthalate metabolites with inflammatory cytokines. The median concentrations of phthalate metabolites ranged from 2.74 to 107.22ng/mL. The mean levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were 0.78 ± 0.21pg/mL and 0.34 ± 0.26pg/mL, respectively. The generalized linear model results revealed that monobutyl phthalate (MBP) was weakly but significantly positively correlated with TNF-α. According to gender and further stratified analysis, the results showed that MBP and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) were weakly but significantly positively correlated with TNF-α and IL-1β only among females. Furthermore, the moderating effects analysis results indicated that rMEQ scores have a negative moderating role among MBP, MEOHP and TNF-α. Phthalate exposure was significantly positively correlated with inflammatory cytokines in young adults, and rMEQ scores played a negative moderating role in this association. This study has the potential to offer useful insights for the prevention and control of chronic inflammation among young adults.

Keywords: Chronotype; Inflammatory cytokines; Phthalate metabolites; Young adults.

摘要

尽管先前的研究表明邻苯二甲酸酯暴露与年轻人的炎症有关，但通过清晨型与夜晚型量表（reduced Morning and Evening Questionnaire，rMEQ）测量的睡眠时型是否在邻苯二甲酸酯暴露与炎症的关联中起到调节/中介作用，目前知之甚少。为填补这些空白，本研究考察了中国年轻人邻苯二甲酸酯代谢物与炎症细胞因子的关联，并探讨了rMEQ评分在该关联中的调节作用。2019年4—5月，从合肥和上饶两市的2所大学招募了1179名年轻人。其中，1135人完成了有效的自填问卷，1012人提供了足够的尿液样本用于邻苯二甲酸酯代谢物分析，744人提供了空腹血液样本用于检测炎症细胞因子水平。采用高效液相色谱-串联质谱法测定尿液中邻苯二甲酸酯代谢物的浓度。利用液相蛋白悬浮芯片检测仪检测上清液中炎症细胞因子的水平。采用rMEQ评分作为睡眠时型的衡量指标。采用广义线性模型分析邻苯二甲酸酯代谢物与炎症细胞因子的关联。采用调节效应分析来检验rMEQ评分是否调节邻苯二甲酸酯代谢物与炎症细胞因子的关联。邻苯二甲酸酯代谢物的中位浓度范围为2.74～107.22 ng/mL。TNF-α和IL-1β的平均水平分别为0.78 ± 0.21 pg/mL和0.34 ± 0.26 pg/mL。广义线性模型结果显示，MBP与TNF-α呈弱但显著的正相关。根据性别进一步分层分析后，结果显示，仅在女性中，MBP和MEOHP与TNF-α和IL-1β呈弱但显著的正相关。此外，调节效应分析结果表明，rMEQ评分在MBP、MEOHP与TNF-α的关系中起到负向调节作用。邻苯二甲酸酯暴露与年轻人炎症细胞因子呈显著正相关，且rMEQ评分在该关联中起到负向调节作用。本研究有可能为年轻人慢性炎症的预防和控制提供有益的见解。

关键词：邻苯二甲酸酯代谢物，炎症细胞因子，睡眠时型，年轻人