摘要
为进一步了解金铃子散毒性影响的代谢特征,探索金铃子散在治疗过程中对未知生物通路的作用。该实验通过以金铃子散3组剂量的水煎剂对大鼠肝肾的影响,来研究金铃子散对大鼠体内代谢组改变的特点和规律。首先对给药2周和给药后1周大鼠尿液和血清样本采用质谱分析方法,通过XCMS在线分析大鼠正负模式离子检测谱,对代谢谱分析的代谢物进行鉴定,结果得到44个差异性物质。最后以Met PA对液质实验中筛选出的代谢物组进行代谢通路富集和分析,结果得到:类固醇激素合成代谢途径,戊糖和葡萄糖醛酸转换,赖氨酸代谢,谷胱甘肽代谢和抗坏血酸代谢5条相关的代谢通路。由代谢网络图可以看出,与毒性相关的通路主要和生物体赖氨酸代谢、葡萄糖醛酸转化及激素代谢有关,尤其是赖氨酸和谷胱甘肽的代谢失衡,造成机体能量代谢或氧化应激调节的紊乱,产生大鼠体内的损伤。从金铃子散低、中、高3组剂量的亚急性毒性实验结果观察发现,金铃子散19.7 g·kg^(-1)和39.4 g·kg^(-1)剂量组造成了明显的毒性作用,说明金铃子散在生物体内可产生毒性作用,且毒性随着给药剂量的增加而增加,造成不可逆的机体损伤。
To further understand the metabolic characteristics of Jinlingzi powder toxicity effect in rats and explore the effect of Jinlingzi powder on unknown biological pathways in the treatment process. In this experiment,the effect of three doses of Jinlingzi powder decoction on rat liver and kidney was investigated to explore the characteristics and rules of Jinlingzi powder on in vivo metabonomic changes in rats. First,urine and serum samples of the rats were used for LC-MS analysis. Under the XCMS online analysis,44 differential substances were found in the identification of metabolites. Finally,Metpa was used for metabolic pathways enrichment and analysis,and five related metabolic pathways were obtained: steroid hormone biosynthesis,tryptophan metabolism,pentose and glucuronate interconversions,ascorbate and aldarate metabolism,as well as glutathione metabolism. Metabolic network diagram showed that the toxicity-related pathways were mainly associated with lysine metabolism in living organisms,glucuronic acid conversion,and hormone metabolism,especially the metabolism imbalance of lysine and glutathione would result in the disorder of energy metabolism or oxidative stress regulation,and thus inducing the damage in rats. Subacute toxicity test results for three doses groups( low,middle and high doses) showed that,Jinlingzi powder with doses of 19. 7 g·kg^(-1)and 39. 4 g·kg^(-1)caused obvious toxic effect,indicating Jinlingzi powder could produce toxic effect in vivo in a dose-dependent manner,and cause irreversible damage to the body.
作者
沈淑洁
水素芳
肖炳坤
杨建云
黄荣清
SHEN Shu-jie SHUI Su-fang XIAO Bing-kun YANG Jian-yun HUANG Rong-qing(Beijing Institute of Radiation Medicine, Belting 100850, China Medical University of Anhui,' Hefei 230032, China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2017年第4期777-782,共6页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(21375147)
北京自然科学基金项目(7142125)
国家"重大新药创制"科技重大专项(2012ZX09301003-001-010)