氰化物急性中毒大鼠的血浆代谢组学研究  

Plasma metabolomics changes in acute cyanide poisoning rats

作　　者：贾娟[1,2,3] 王超忍 尉志文 曹洁[1,2,3] 牛卫芬 张枫林[1,2,3] 严江伟 贠克明 Jia Juan;Wang Chaoren;Hei Zhiwen;Cao Jie;Niu Weifen;Zhang;Fenglin;Yan Jiangwei;Yun Keming(Shanxi Medical University,Jinzhong Shanxi 030600;Key Laboratory of Forensic Toxicology Analysis,Ministry of Public Security,Jinzhong Shanxi 030600;Key Laborary of forensic Medicine in Shanxi Province,Jinzhong Shanxi 030600;Traffic Police Detachment of Xi'an Public Security Bureau,Xi'an Shanxi,710065)

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 [3]法医学山西省重点实验室,山西晋中030600 [4]西安市公安局交通警察支队,陕西西安710065

出　　处：《中国法医学杂志》2023年第5期525-529,536,共6页Chinese Journal of Forensic Medicine

基　　金：国家自然科学基金资助(82130056,82030058)。

摘　　要：目的利用代谢组学技术研究急性氰化物中毒大鼠血浆中小分子代谢物的变化,寻找差异代谢物,分析与氰化物中毒相关的代谢途径,进而研究氰化物中毒的机制。方法将健康SD大鼠随机分为空白对照组和实验组(雄性,每组5只),实验组灌胃3.2 mg/kg(1/2LD50)氰化钾溶液建立氰化物急性中毒模型,对照组灌胃等剂纯水,灌胃后分别于45 min,24 h,120 h眼眶静脉采血,通过高效液相色谱-飞行时间质谱采集大鼠血浆代谢谱,根据主成分分析(PCA)、正交偏最小二乘判别分析(OPLS-DA)以及t检验和变异倍数分析筛选差异代谢物,并通过KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库进行代谢通路分析。结果筛选出19个与氰化物中毒相关的差异代谢物,且随时间变化差异代谢物的种类存在差异,主要涉及胆汁分泌、氨基酸代谢等共11条代谢通路。结论可将牛磺胆酸盐和牛磺鹅胆酸盐作为氰化物中毒潜在生物标志物,马尿酸可以作为两者的辅助指标,也可根据差异代谢物的不同进行服药时间的初步推断。氰化物会对机体酶的活性和能量代谢过程产生影响,且可能造成肝脏损伤。Objective Metabolomics technology was used to study the changes of metabolic profile in the plasma of rats with acute cyanide poisoning,to find differential metabolites and analyze the related metabolic pathways,and to study the mechanism of cyanide poisoning at the metabolic level.Methods Healthy SD rats were randomly divided into blank control group and experimental group(male,5 in each group).Rats in the experimental group were intragastric administered 3.2 mg/kg(1/2LDso)potassium cyanide solution to establish a model of acute cyanide poisoning.Rats in the control group were administered water.Blood samples were collected from orbital veins at 45 min,24 h and 120 h after intragastric administration.The plasma metabolism profile of rats was explored by UPLC-Triple TOF-MS.Differential metabolites were screened by PCA,OPLS-DA,T test and FC analysis,and metabolic pathways were analyzed using KEGG(Kyoto Encyclopedia of Genes and Genomes)database.Results Nineteen differential metabolites related to cyanide poisoning were screened out,and the types of differential metabolites varied over time,mainly involving 1l metabolic pathways such as bile secretion and amino acid metabolism.Conclusion Taurocholate and taurochenocholate can be considered as potential biomarkers of cyanide poisoning,and hippuric acid can be used as an auxiliary indicator of them.According to the different metabolites,the time of drug administration can also be preliminarily inferred.Cyanide can affect the activity of the enzymes and energy metabolism in the body and may cause liver damage.

关 键 词：氰化物中毒 生物标志物 超高效液相色谱-飞行时间质谱 血浆代谢组学 

分 类 号：D918.93[政治法律—法学]