Abstract：
Lead poisoning is often considered a traditional disease; however, the specific mechanism of toxicity remains unclear. The study of Pb-induced alterations in cellular metabolic pathways is important to understand the biological response and disorders associated with environmental exposure to lead. Metabolomics studies have recently been paid considerable attention to understand in detail the biological response to lead exposure and the associated toxicity mechanisms. In the present study, wild rodents collected from an area contaminated with lead (N = 18) and a control area (N = 10) were investigated. This was the first ever experimental metabolomic study of wildlife exposed to lead in the field. While the levels of plasma phenylalanine and isoleucine were significantly higher in a lead-contaminated area versus the control area, hydroxybutyric acid was marginally significantly higher in the contaminated area, suggesting the possibility of enhancement of lipid metabolism. In the interregional least-absolute shrinkage and selection operator (lasso) regression model analysis, phenylalanine and isoleucine were identified as possible biomarkers, which is in agreement with the random forest model. In addition, in the random forest model, glutaric acid, glutamine, and hydroxybutyric acid were selected. In agreement with previous studies, enrichment analysis showed alterations in the urea cycle and ATP-binding cassette transporter pathways. Although regional rodent species bias was observed in this study, and the relatively small sample size should be taken into account, the present results are to some extent consistent with those of previous studies on humans and laboratory animals.
摘要：
铅中毒通常被认为是一种传统疾病；然而，毒性的具体机制尚不清楚.研究铅诱导的细胞代谢途径变化对于了解与环境暴露于铅相关的生物反应和疾病很重要。最近，代谢组学研究引起了人们的广泛关注，以详细了解对铅暴露的生物学反应以及相关的毒性机制。在本研究中,调查了从铅污染区域（N=18）和控制区（N=10）收集的野生啮齿动物。这是该领域首次对暴露于铅的野生动物进行的实验性代谢组学研究。虽然铅污染地区的血浆苯丙氨酸和异亮氨酸水平明显高于对照组，在污染区，羟基丁酸的含量略高，提示脂质代谢增强的可能性。在区域间最小绝对收缩和选择算子(Lasso)回归模型分析中，苯丙氨酸和异亮氨酸被鉴定为可能的生物标志物，这与随机森林模型是一致的。此外,在随机森林模型中，戊二酸,谷氨酰胺,选择羟基丁酸。与以前的研究一致，富集分析显示尿素循环和ATP结合盒转运蛋白途径发生改变.尽管在这项研究中观察到了区域啮齿动物物种偏见，应该考虑到相对较小的样本量，目前的结果在一定程度上与以前对人类和实验动物的研究一致。
