背景:关于重金属暴露和肝损伤的流行病学研究主要是横断面的,缺乏纵向数据和潜在机制的探索。
方法:我们于2016年至2019年在中国东北地区进行了重复措施研究,涉及322名参与者。线性混合模型(LMM)和贝叶斯核机回归(BKMR)用于探索个体和混合血液金属浓度之间的关联[铬(Cr),镉(Cd),钒(V),锰(Mn),铅(Pb)]和肝功能生物标志物[丙氨酸氨基转移酶(ALT),天冬氨酸转氨酶(AST),白蛋白(ALB),球蛋白(GLB),总蛋白(TP)]。中介和富集分析用于确定炎症反应是否是重金属诱导的肝损伤的关键途径。
结果:我们总共获得了958个观察结果。LMM和BKMR的结果表明,个体和混合重金属与肝功能生物标志物之间存在显着关联。纵向分析显示Cd与ALT的年增长率之间存在关联(β=2.61;95%CI:0.97,4.26),ALB的年下降率(β=-0.21;95%CI:-0.39,-0.03),锰和GLB的年增长率(β=0.38;95%CI:0.05,0.72),和V与ALB/GLB的年下降率(β=-1.15;95%CI:-2.00,-0.31)。中介分析显示高敏C反应蛋白(hsCRP)介导了Cd与AST的关系,TP,调解效果分别为27.7%和13.4%,分别。此外,基因本体论和京都百科全书的基因和基因组富集分析的结果支持炎症反应途径的作用。
结论:我们的研究结果表明,重金属暴露会导致肝损伤,炎症反应可能是这一过程中的关键途径。这项研究为理解重金属引起的肝损伤提供了新的视角,并为针对重金属引起的健康损害的预防措施提供了见解。
BACKGROUND: Epidemiological studies on heavy metal exposure and liver injury are predominantly cross-sectional, lacking longitudinal data and exploration of potential mechanisms.
METHODS: We conducted a repeated-measures study in Northeast China from 2016 to 2019, involving 322 participants. Linear mixed models (LMM) and Bayesian kernel machine regression (BKMR) were employed to explore the associations between individual and mixed blood metal concentrations [chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), lead (Pb)] and liver function biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLB), total protein (TP)]. Mediation and enrichment analyses were used to determine whether the inflammatory response is a critical pathway for heavy metal-induced liver damage.
RESULTS: We obtained a total of 958 observations. The results from LMM and BKMR indicated significant associations between individual and mixed heavy metals and liver function biomarkers. Longitudinal analysis revealed associations between Cd and the annual increase rate of ALT (β = 2.61; 95% CI: 0.97, 4.26), the annual decrease rate of ALB (β = -0.21; 95% CI: -0.39, -0.03), Mn and the annual increase rate of GLB (β = 0.38; 95% CI: 0.05, 0.72), and V and the annual decrease rate of ALB/GLB (β = -1.15; 95% CI: -2.00, -0.31). Mediation analysis showed that high-sensitivity C-reactive protein (hsCRP) mediated the associations between Cd and AST, TP, with mediation effects of 27.7% and 13.4%, respectively. Additionally, results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses supported the role of inflammatory response pathways.
CONCLUSIONS: Our findings indicate that heavy metal exposure leads to liver damage, with the inflammatory response potentially serving as a crucial pathway in this process. This study offers a novel perspective on understanding heavy metal-induced liver injury and provides insights for preventive measures against the health damage caused by heavy metals.