醋甘遂成分群B,C对正常大鼠粪便代谢组学的研究

基于代谢组学方法,对给予醋甘遂不同成分群(B,C)前后大鼠的粪便代谢物进行比较研究,探求与醋甘遂毒性相关的差异性代谢物和代谢通路,揭示醋甘遂的毒性作用机制。采用快速液相色谱串联四极杆飞行时间质谱(UFLC-Q-TOF-MS)技术,对大鼠粪便样本进行测定,结合主成分分析(PCA)和偏最小二乘-判别分析(OPLS-DA)等多种方法筛选并鉴定与醋甘遂毒性相关的生物标志物,并采用t检验进行单变量统计分析,考察给予醋甘遂成分群B,C后正常大鼠粪便这些生物标志物的含量变化,揭示醋甘遂成分群B,C对大鼠粪便代谢组的影响程度,并结合基于MetaboAnalyst数据库的代谢通路分析探求醋甘遂成分群B,C的毒性作用机制。结果显示,与空白组相比,醋甘遂成分群B和C组大鼠粪便样本代谢组发生了明显改变,且醋B组改变程度更大,发现并鉴定了16种醋甘遂毒性潜在生物标志物及5条相关代谢通路。醋甘遂的毒性作用可能与色氨酸代谢、初级胆汁酸生物合成、氨基糖和核苷酸糖代谢、嘌呤代谢和缬氨酸,亮氨酸和异亮氨酸降解等代谢通路的紊乱有关。该研究为醋甘遂的临床安全应用提供了科学依据。

Effect of chemical ingredients B and C in Kansui stir-baked with vinegar on fecal metabolomics in rats

To reveal the toxic mechanism of Kansui stir-baked with vinegar(VEK),conducta comparative study on the metabolites of fecal samples of rats before and after being treated with chemical constituents group B and C(VEKB/VEKC)extracted from VEK by metabolomics approach.The fecal samples of each group were analyzed using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UFLC-Q-TOF-MS).Then the data was processed by principal component analysis(PCA)and partial least square discriminant analysis(OPLS-DA)to screen and identify biomarkers relating to the toxicity of VEK.Besides,t-test was adopted for univariate statistical analysis,so as to study the changes of these biomarkers in drug groups before and after being treated with VEKB/VEKC and explore the effect of VEKB/VEKC on the metabolism of rat feces.Furthermore,the toxic mechanism of VEKB/VEKC was explored based on the results of the metabolic pathway analysis.The results displayed that compared with control group,the metabolism of fecal samples of VEKB and VEKC treated groups show obvious changes,and the VEKB treated group show more significant changes.A total of 16 potential biomarkers and 5 metabolic pathways relating to the toxicity of VEK were found and identified.And the toxicity of VEK might be associated with the disorder of such metabolic pathways as tryptophan metabolism,primary bile acid biosynthesis,amino sugar and nucleotide sugar metabolism,purine metabolism,and degradation of valine,leucine and isoleucine.This study provides a scientific basis for the clinical safety application of VEK.