摘要
目的通过非靶向代谢组学研究滇乌头碱慢性中毒大鼠尿液代谢谱的变化,探讨滇乌头碱中毒的可能机制。方法建立滇乌头碱大鼠中毒模型,采用基于超高效液相色谱-四极杆飞行时间质谱(ultra per⁃formance liquid chromatography-quadrupole-time of flight mass spectrometry,UPLC-QTOF-MS)技术的代谢组学方法,获得尿液代谢轮廓,应用主成分分析(principal component analysis,PCA)、正交偏最小二乘法-判别分析(orthogonal projections to latent structures-discriminant analysis,OPLS-DA),依据变量投影重要度(variable importance in projection,VIP)>1、变化倍数(fold change,FC)>3或<0.33、P<0.05筛选出与滇乌头碱毒性相关的潜在生物学标志物,通过MetaboAnalyst网站进行代谢通路分析,同时观察相关组织的病理学改变。结果筛选出L-异亮氨酸等16个潜在生物学标志物,主要涉及缬氨酸、亮氨酸与异亮氨酸的生物合成、降解,戊糖和葡萄糖醛酸的相互转化,丙酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢,酪氨酸代谢等6条代谢通路。病理学研究可见滇乌头碱导致的大鼠神经系统、肝和心脏毒性病变。结论滇乌头碱可能通过影响氨基酸和糖代谢,产生神经系统、肝和心脏等毒性。
Objective To explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted me-tabolomics.Methods A rat model of Yunaconitine poisoning was established,and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile.Princi-pal component analysis(PCA),orthogonal projections to latent structures-discriminant analysis(OPLS-DA),variable importance in projection(VIP)value greater than 1,fold change(FC)value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine.The metabolic pathway analysis was performed through the MetaboAna-lyst website and pathological changes of related tissues were observed.Results Sixteen potential bio-markers including L-isoleucine were screened,which mainly involved six metabolic pathways including the biosynthesis and degradation of valine,leucine and isoleucine,pentose and glucuronate interconver-sions,and propanoate metabolism,alanine,aspartate and glutamate metabolism,tyrosine metabolism.Pathological studies showed that rat toxic change in nervous system,liver and cardiac caused by Yu-naconitine.Conclusion Yunaconitine may cause neurotoxicity,hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.
作者
周惠黠
刘欢
韩雪
聂胜洁
张荣平
于建云
李树华
ZHOU Hui-xia;LIU Huan;HAN Xue;NIE Sheng-jie;ZHANG Rong-ping;YU Jian-yun;LI Shu-hua(School of Forensic Medicine,Kunming Medical University,Kunming 650500,China;Judicial Expertise Center,Kunming Medical University,Kunming 650500,China;School of Medicine,Kunming Medical University,Kunming 650500,China;School of Traditional Chinese Pharmacy,Yunnan University of Traditional Chinese Medicine,Kunming 650500,China)
出处
《法医学杂志》
CAS
CSCD
2021年第5期653-660,共8页
Journal of Forensic Medicine
基金
云南省创新团队资助项目(202005AE160004)
国家重点研发计划资助项目(2018YFC0807201-4)。
关键词
法医毒理学
代谢组学
中毒
滇乌头碱
超高效液相色谱-四极杆-飞行时间质谱
尿液
大鼠
forensic toxicology
metabolomics
poisoning
Yunaconitine
ultra performance liquid chromatography coupled with quadrupole-time of flight-mass spectrometry
urine
rats
