由Tl和Cd驱动的NEM混合物与肝功能损害相关，脂质谱可能介导这些效应

Associations of non-essential metal/metalloids and their mixture with liver function in Chinese older adults: the mediating roles of lipid profiles

中国老年人非必需金属/类金属及其混合物与肝功能的关系：血脂特征的中介作用

Authors：Xuqiu Cheng, Wenyuan Liu, Ziwei Tian Jinqi Yan, Xianglong Liu, Qiang Liu, Yan Zhang, Yuan Wang, Bing Hu, Jun Wang, Fangbiao Tao, Linsheng Yang

Source：Environmental Pollution

DOI: 10.1016/j.envpol.2025.126207

Abstract

The liver is vulnerable to damage from environmental pollutants, but evidence on the effects of non-essential metal/metalloid (NEM) mixture on liver function and their mechanisms remains limited. The study aimed to explore the correlations between individual NEMs and their combinations with liver function, and the mediating roles of lipid profiles. The research involved 2642 individuals aged 60 and older in China. Urine concentrations of arsenic (As), cesium (Cs), barium (Ba), thallium (Tl), and cadmium (Cd) were analyzed using ICP-MS. Liver function was assessed based on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). To evaluate the individual and combined effects of these NEMs on liver function, linear regression, restricted cubic splines (RCS), weighted quantile sum (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models were utilized. Mediation analyses were conducted to explore the potential role of lipid profiles in NEM-liver function relations. Adjusted linear regression revealed positive associations of Tl with ALT (β = 0.044, 95 % CI: 0.022 to 0.066) and AST (β = 0.019, 95 % CI: 0.004 to 0.035), and negative associations of Cs (β = -0.015, 95 % CI: -0.020 to -0.010), Tl (β = -0.010, 95 % CI: -0.015 to -0.005), and Cd (β = -0.019, 95 % CI: -0.024 to -0.014) with ALB. The RCS model confirmed these linear relationships. Mixture models consistently demonstrated a positive association between the NEM mixture and ALT/AST, primarily driven by Tl, and a negative association with ALB, predominantly influenced by Cd. Mediation analyses suggested triglycerides and total cholesterol partially mediated the associations between Tl, the NEM mixture, and liver function. In conclusion, the NEM mixture, mainly driven by Tl and Cd, is linked to liver function impairment, with lipid profiles potentially mediating these effects. More research is needed to confirm these findings and clarify the mechanisms.

Keywords: Liver function; Mixture model; Non-essential metal; Older adults.

摘要：

肝脏容易受到环境污染物的损害，但关于非必需金属/准金属(NEM)混合物对肝功能的影响及其机制的证据仍然有限。本研究旨在探索单个NEMs及其组合与肝功能的相关性，以及脂质谱的中介作用。这项研究涉及中国2642名60岁及以上的老人。使用ICP-MS分析尿中砷(As)、铯(Cs)、钡(Ba)、铊(Tl)和镉(Cd)的浓度。根据丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和白蛋白(ALB)的水平评估肝功能。为了评估这些nem对肝功能的单独和综合影响，使用了线性回归、受限三次样条(RCS)、加权分位数总和(WQS)、分位数g计算(QGC)和贝叶斯核机器回归(BKMR)模型。进行了中介分析，以探索血脂谱在NEM和肝功能关系中的潜在作用。校正线性回归显示Tl与ALT (β = 0.044，95 % CI: 0.022至0.066)和AST (β = 0.019，95 % CI: 0.004至0.035)呈正相关，与Cs (β = -0.015，95 % CI: -0.020至-0.010)、Tl (β = -0.010，95 % CI: -0.015至-0.005)呈负相关。RCS模型证实了这些线性关系。混合物模型始终显示NEM混合物和ALT/AST之间的正相关，主要由Tl驱动，和与ALB的负相关，主要受Cd影响。中介分析表明甘油三酯和总胆固醇部分介导了Tl、NEM混合物和肝功能之间的联系。总之，主要由Tl和Cd驱动的NEM混合物与肝功能损害相关，脂质谱可能介导这些效应。需要更多的研究来证实这些发现并阐明其机制。

关键词：肝功能；混合物模型；非必需金属；老年人