Fei Qian-Qian, Wei Ying-Jie, Wang Jing, Huang Yi-Ping, Chen Yan, Chen Bin
the Third Clinical Medical College (Affiliated Provincial Hospital of Integrated Traditional Chinese Medicine and Western Medicine) ,Nanjing University of Chinese Medicine,Key Laboratory for Traditional Chinese Medicine Drug Release System under State Administration of Traditional Chinese Medicine,Jiangsu Province Academy of Traditional Chinese Medicine Nanjing 210028,China.
Zhongguo Zhong Yao Za Zhi. 2019 Sep;44(17):3798-3805. doi: 10.19540/j.cnki.cjcmm.20190429.503.
Based on metabolomics,the metabolites of larvae zebrafish with overdose of Panax notoginseng saponins( PNS) were compared with those in normal group of larvae zebrafish to investigate the possible toxicity mechanism of overdose PNS in larvae zebrafish. An experimental animal model of long-term toxicity induced by PNS overdose was established by administering 1-6 dpf at low,medium and high doses of PNS,respectively. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry( UPLC-Q-TOF-MS) technique was combined with principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA) to screen and identify biomarkers associated with toxicity,and then the MetaboAnalyst database was used to analyze metabolism-related pathways. The results showed that the metabolites of each group could be distinguished distinctly,and they deviated more from the normal group in a time and dose dependent manner. Twenty-nine potential biomarkers related to toxicity( VIP>1,P<0. 05) were identified preliminarily,mainly involving six metabolic pathways. From the metabonomics point of view,the toxicity mechanism of overdose PNS may be related to the disorders of lipid metabolism,amino acid metabolism and energy metabolism.
基于代谢组学，将过量三七总皂苷（PNS）处理的斑马鱼幼鱼代谢产物与正常斑马鱼幼鱼组进行比较，以探究过量PNS对斑马鱼幼鱼可能的毒性机制。分别在斑马鱼胚胎1至6天以低、中、高剂量PNS建立PNS过量诱导的长期毒性实验动物模型。采用超高效液相色谱-四极杆-飞行时间质谱（UPLC-Q-TOF-MS）技术结合主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）筛选和鉴定与毒性相关的生物标志物，然后利用MetaboAnalyst数据库分析代谢相关通路。结果表明，各组代谢产物能够明显区分，且随时间和剂量依赖性地与正常组差异增大。初步鉴定出29个与毒性相关的潜在生物标志物（VIP>1，P<0.05），主要涉及6条代谢途径。从代谢组学角度来看，过量PNS的毒性机制可能与脂质代谢、氨基酸代谢和能量代谢紊乱有关。
