中药毒性的代谢组学研究(Ⅱ):吡咯里西啶类生物碱的肝肾毒性  

Metabonomic Study on the Toxicity of Chinese Medicine(Ⅱ): Hepato-nephrotoxicity of Pyrrolizidine Alkaloids

作　　者：祁乃喜[1] 刘玉梅[2] 何翠翠[2] 华嘉[2] 李建新[2] 

机构地区：[1]南京中医药大学附属医院,江苏南京210029 [2]南京大学化学化工学院生命分析化学国家重点实验室,江苏南京210093

出　　处：《南京中医药大学学报》2012年第5期448-451,共4页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家重点基础研究发展计划("973"计划)(2007CB714504)

摘　　要：目的分析经中药千里光中吡咯里西啶类生物碱染毒后大鼠尿液内源性代谢产物的变化,研究该类生物碱的肝肾毒性,为中药毒性评价提供简单可靠的方法。方法利用生物核磁共振技术分析对照组,吡咯里西啶类生物碱口服给药组的大鼠7d的尿液、结合模式识别技术和主成分分析法评价吡咯里西啶类生物碱对大鼠尿液内源性代谢物的影响,探讨吡咯里西啶类生物碱的肝肾毒性。结果与对照组相比,口服吡咯里西啶类生物碱引起大鼠尿中牛磺酸,氧化三甲胺以及二甲基甘氨酸含量的持续增高,说明对肝脏及肾脏造成了损伤,提示吡咯里西啶类生物碱存在肝肾毒性。结论从代谢组学的角度可以诠释中药千里光的肝肾毒性,提示代谢组学方法可为传统中药毒性研究提供新的手段。OBJECTIVE To study the hepato-nephrotoxicity of pyrrolizidine alkaloids isolated from Herba Senecionis Scandentis via analyzing changes of endogenous metabolites in rat urines after administration of the alkaloids,and provide a simple and reliable method for toxicity evaluation of traditional Chinese medicine（TCM）.METHODS The hepato-nephrotoxicity of the alkaloids was explored through analyzing urines collected from rats in both the control and pyrrolizidine alkaloids orally administrated groups in 7 days by bio-nuclear magnetic resonance（bio-NMR）,and evaluating pyrrolizidine alkaloids＇ influences on endogenous metabolites in urine by pattern recognition technique and principal component analysis（PCA）.RESULTS Compared with the control group,the continuous increase of taurine,trimethylamine-N-oxide（TMAO） and dimethylglycine（DMG） in urines of pyrrolizidine alkaloids orally administrated group proved that alkaloids had caused damages to the liver and kidney,which indicated the hepato-nephrotoxicity of pyrrolizidine alkaloids.CONCLUSION The hepato-nephrotoxicity of Herba Senecionis Scandentis could be explained from the metabonomics point of view,suggesting that the metabonomic method might provide a new approach for the evaluation of the toxicity of TCM.

关 键 词：生物核磁共振 代谢组学 千里光 吡咯里西啶类生物碱 毒性 

分 类 号：R285.5[医药卫生—中药学]