基于代谢组学技术筛选甲氰菊酯中毒大鼠生物标志物  

Metabolomics-based screening of biomarkers for fenpropathrin-exposed rats

作　　者：杨倩[1,2] 王涛 郭芳[1,2] 宁玉蝶 贠克明[1,2] 尉志文 Yang Qian;Wang Tao;Guo Fang;Ning yudie;Yun keming;Wei zhiwen(Shanxi Medical University,Jinzhong,Shanxi 030600;Key Laboratory of Forensic Toxicological Analysis,Ministry of Public Security,Jinzhong,Shanxi 030600)

机构地区：[1]山西医科大学,山西晋中030600 [2]法庭毒物分析公安部重点实验室,山西晋中030600

出　　处：《中国法医学杂志》2024年第3期308-314,共7页Chinese Journal of Forensic Medicine

基　　金：山西省基础研究计划青年项目(202103021223236);山西省自然科学研究面上项目(202103021224233)。

摘　　要：目的通过代谢组学技术,分析甲氰菊酯染毒大鼠血浆中的代谢产物变化,寻找潜在的生物标志物,以便在法医学上对甲氰菊酯中毒进行鉴定。方法SD大鼠随机分成1/8LD50甲氰菊酯组(用20.5 mg/kg的甲氰菊酯灌胃)、1/4LD50甲氰菊酯组(用41 mg/kg的甲氰菊酯灌胃)和对照组(用生理盐水灌胃),灌胃24 h后收集大鼠眼眶血样。使用超高效液相色谱-飞行时间质谱联用技术,对血浆中存在的内源性小分子代谢产物进行检测。使用SIMCA14.1软件进行多维统计分析,根据OPLS-DA模型中的变量权重重要性排序值(VIP),并结合p<0.05的统计显著性,筛选出甲氰菊酯染毒大鼠血浆中差异代谢物。最后,对这些差异代谢物进行通路分析。结果对照组和实验组大鼠的血浆代谢物水平差异显著,并筛选出17种可以鉴别甲氰菊酯中毒的生物标志物,主要影响嘌呤代谢、丙氨酸、天冬氨酸和谷氨酸代谢、精氨酸生物合成、不饱和脂肪酸的生物合成和嘧啶代谢。结论甲氰菊酯可改变大鼠体内代谢物的组成,通过筛选出的差异标志物,可以在法医学上为甲氰菊酯中毒相关案件提供支持性证据。Objective Metabolomics was used to analyze the changes of metabolites in the plasma of Fenpropathrincontaminated rats to find potential biomarkers for forensic identification of Fenpropathrin poisoning.Methods SD rats in the two experimental groups were given 20.5 mg/kg and 41 mg/kg doses of fenpropathrin respectively by gavage.The rats in the control group were given equivalent volume of normal saline.The angular vein blood of rats was collected 24 hours after gavage,and endogenous small molecule metabolites in plasma were investigated by ultra-performance liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS).The data was processed by SIMCA14.1.The differential metabolites in plasma of fenpropathrin-infected rats were screened out according to the Variable Importance in Projection(VIP)and p<0.05 in the OPLS-DA model.Finally,the pathways were analyzed.Results There were significant differences in plasma metabolite levels between the control group and the experimental group,and 17 biomarkers were selected to identify whether the rats had received fenpropathrin,which mainly affected purine metabolism,Alanine,aspartate and glutamate metabolism,arginine biosynthesis,biosynthesis of unsaturated fatty acids and pyrimidine metabolism.Conclusion Fenpropathrin can change the composition of metabolites in rats,and the differential markers screened can provide supportive forensic evidence for cases related to deltamethrin poisoning.

关 键 词：法医毒理学 生物标志物 甲氰菊酯 代谢组学 超高效液相色谱-飞行时间质谱 

分 类 号：D918.93[政治法律—法学]