职业性慢性铅中毒患者血清代谢组学研究  

Serum metabolomics study in patients with occupational chronic lead poisoning

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作  者:刘炳辰 徐金 苏瑶[1] 王炜[1] 秦宏[1] 孙纳[1] 李春平[1] LIU Bingchen;XU Jin;SU Yao;WANG Wei;QIN Hong;SUN Na;LI Chunping(The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University,Wuxi Center for Disease Control and Prevention,Wuxi,Jiangsu 214023,China)

机构地区:[1]无锡市疾病预防控制中心(南京医科大学附属无锡疾病预防控制中心),江苏无锡214023

出  处:《中国职业医学》2024年第5期496-504,共9页China Occupational Medicine

基  金:江苏省卫生健康委员会科学研究项目(M2020036);无锡市卫生健康委面上项目(M202169)。

摘  要:目的 采用基于非靶向代谢组学技术研究职业性慢性铅中毒患者血清中差异代谢物(DMs)的变化情况,筛选差异代谢通路。方法 采用判断抽样方法,选择14例职业性慢性铅中毒患者为中毒组,选择14名无职业病危害接触史的健康对照人群为对照组;采集2组人群血清,采用基于超高效液相色谱串联质谱法的非靶向代谢组学技术检测2组人群的血清代谢物表达水平,采用主成分分析法、偏最小二乘判别分析和正交最小偏二乘判别分析筛选DMs,并探索相关代谢通路。结果 中毒组人群血铅水平高于对照组(中位数:359.59 vs 5.04μg/L,P<0.01)。中毒组与对照组人群的血清代谢物差异显著。经正负离子模式合并后,中毒组人群血清中共筛选出89种DMs;其中,50种表达上调,39种表达下调。与对照组比较,中毒组人群血清中的DMs富集于精氨酸生物合成、ABC转运蛋白、嘌呤代谢、恶性肿瘤中的胆碱代谢、甘油磷脂代谢和醚脂代谢等通路(P值均<0.05)。结论 职业性慢性铅中毒患者血清代谢谱发生了异常改变。精氨酸生物合成、ABC转运蛋白、嘌呤代谢、胆碱代谢、甘油磷脂代谢和醚脂代谢等代谢通路可能参与了铅中毒的发生发展。Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics,and to screen differential metabolic pathways.Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group,and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method.Serum of the individuals from the two groups was collected.Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups.Differential metabolites(DMs)were screened by the principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis,and related metabolic pathways were explored.Results The blood lead level in the poisoning group was higher than that in the control group(median:359.59 vs 5.04µg/L,P<0.01).There were significant differences in serum metabolites between the poisoning group and control group.After the combination of results from the positive and negative ion patterns,a total of 89 DMs were screened in serum of patients in the poisoning group,including 50 upregulated and 39 downregulated metabolites compared with the control group.The serum DMs of poisoning group were mainly enriched in arginine biosynthesis,ABC transporter,purine metabolism,choline metabolism in malignant tumor,glycerophospholipid metabolism and ether lipid metabolism compared with the control group(all P<0.05).Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning.The metabolic pathways such as arginine biosynthesis,ABC transporter,purine metabolism,choline metabolism,glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

关 键 词: 铅中毒 慢性中毒 血清 代谢组学 代谢物 代谢通路 

分 类 号:R135.1[医药卫生—劳动卫生] R114[医药卫生—公共卫生与预防医学]

 

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