代谢组学筛选纳米二氧化钛职业接触血清生物标志物  

Screening serum biomarkers for occupational exposure to titanium dioxide nanoparticles using metabolomics

作　　者：陈章健[1] 韩硕 郑湃[1] 刘晓东 贾光[1] CHEN Zhangjian;HAN Shuo;ZHENG Pai;LIU Xiaodong;JIA Guang(School of Public Health,Peking University,Beijing 100191,China;不详)

机构地区：[1]北京大学公共卫生学院,北京100191 [2]北京市化工职业病防治院/北京市职业病防治研究院,北京100093

出　　处：《中国职业医学》2020年第6期633-639,共7页China Occupational Medicine

基　　金：国家重点研发计划项目(2017YFC1600200)。

摘　　要：目的利用代谢组学技术筛选职业接触纳米二氧化钛(TiO_(2))工人的血清生物标志物。方法采用典型抽样方法,选择某纳米TiO_(2)生产企业56名职业性接触TiO_(2)的工人为接触组,以该企业44名无职业性接触TiO_(2)的人员为对照组,采用高效液相色谱-质谱联用技术进行非靶向代谢组学检测,分析2组人员血清代谢物谱的差异,筛选关键的差异代谢物和潜在的生物标志物,通过受试者工作特征(ROC)曲线评价生物标志物敏感性和特异性。结果血清代谢组学分析共检测到血清样品中1 492个质谱峰,经注释和鉴定获得匹配良好的413种代谢物。主成分分析法和正交偏最小二乘法判别分析结果显示,与对照组比较,接触组人群血清中共发现差异代谢物296种(P值均<0.01);其中,代谢物相对表达量升高者265种,下降者31种。ROC曲线分析结果显示,5种代谢物的ROC曲线下面积>0.900,分别为丹参酚A、(5E)-2-羟基-4-氧代苯并五-5-烯-1-基乙酸、三萜皂苷类有机化合物、9,10,13-三羟基硬脂酸和山梨酸。多元线性回归分析结果显示,在调整性别、年龄、体质量指数、吸烟和饮酒等混杂因素的影响后,上述5种代谢物的相对表达量均与纳米TiO_(2)职业接触呈正相关(P值均<0.01)。结论纳米TiO_(2)职业接触可诱导职业接触人群血清代谢物谱改变。血清中以丹参酚A为代表的代谢物可作为纳米TiO_(2)职业接触潜在的生物标志物。Objective To screen the serum biomarkers in workers occupationally exposed to titanium dioxide nanoparticles(TiO_(2) NPs) using metabolomics technology. Methods Using a typical sampling method, 56 workers who have occupationally exposed to TiO_(2) in a TiO_(2) NPs manufacturer were selected as the exposure group and 44 employees without occupational exposure to TiO_(2) were selected as the control group. The high performance liquid chromatography-mass spectrometry technology was used to perform non-targeted metabolomics detection. The difference in serum metabolite profiles of the TiO_(2) NPs exposure group and the control group were analyzed. Key differential metabolites and potential biomarkers were screened. The sensitivity and specificity of biomarkers were assessed through receiver operating characteristic(ROC) curve.Results We detected a total of 1 492 mass spectrum peaks in serum samples by serum metabolomics analysis, and 413 well-matched metabolites were obtained after annotation and identification. The results of principal component analysis and orthogonal partial least squares discriminant analysis showed that a total of 296 differentially expressed metabolites were found in the serum of individuals of the exposure group compared with the control group(all P<0.01). Among them the relative expression of metabolites increased in 265 species and decreased in 31 species. The ROC analysis results showed that the area under the ROC curve of five metabolites exceeded 0.900, and these metabolites included tanacetol A,(5 E)-2-hydroxy-4-oxobenzopenta-5-en-1-ylacetic acid, triterpene saponins organic compounds, 9,10,13-trihydroxystearic acid, and liquoric acid. The multiple linear regression analysis showed that the relative expression of all the five metabolites were positively correlated with occupational exposure to TiO_(2) NPs after adjusting for the influence of confounding factors such as gender, age, body mass index, smoking and drinking(all P<0.01). Conclusion Occupational exposure to TiO_(2) NPs could in

关 键 词：纳米二氧化钛 代谢组学 职业接触 血清 生物标志物 

分 类 号：R135.99[医药卫生—劳动卫生]