摘要
目的基于超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q/TOF-MS)技术探讨广金钱草水提物对肾草酸钙结石大鼠血清中内源性标志物的影响,从血清代谢组学角度阐释广金钱草水提物抗肾草酸钙结石的分子机制。方法将SD雄性大鼠随机分为对照组、模型组、广金钱草组(2.2 g·kg-1),每组10只。灌胃给药1 h后,模型组及广金钱草治疗组再灌胃给予15%乙二醇水溶液,灌胃体积10 mL·kg-1,连续21 d。观察大鼠一般情况并测定体质量;检测大鼠血清尿酸、尿素氮、血清肌酐、血Ca和血Mg等肾功能生化指标;计算大鼠肾脏肥大指数;HE染色观察肾脏组织病理形态。应用UPLC-Q/TOF-MS技术进行血清样品的分离和数据采集,通过主成分分析(PCA)和正交偏最小二乘判别分析法(OPLS-DA)分析广金钱草水提物对内源性代谢物的影响,鉴定肾草酸钙结石模型大鼠的生物标记物和代谢通路,以确定广金钱草对肾草酸钙结石干预作用的代谢途径。结果共筛选和鉴定出与肾草酸钙结石密切相关的16个生物标记物,以及14条代谢通路。广金钱草可能通过对氨基酸代谢、甘油磷脂代谢、泛酸和辅酶A代谢等多条代谢通路发挥调节作用,可回调酪氨酸、色氨酸、苯丙氨酸、异亮氨酸、甜菜碱、尿苷、泛酸等12个代谢物。结论广金钱草水提物抗肾草酸钙结石的作用可能与其通过多条代谢通路改善内源性代谢物的水平,恢复机体正常代谢活动有关。
Objective Desmodii styracifolii herba(DS)has an inhibitory effect on calcium oxalate kidney stones(CKS)and this study aimed to explore the underlying molecular mechanism based on serum metabolic profiles.Methods Rats were randomly divided into three groups:the control group,the model group,and the DS intervention group.Rats were treated by continuously intragastric(ig)administration for 21 days.CKS rat model was induced experimentally by ig administration of 15%ethylene glycol(10 mL·kg-1).Body weight,biochemical indexes,kidney hypertrophy index and histopathological examination were used to evaluate the efficacy of DS after the model was successfully replicated.UHPLC-Q/TOF-MS-based metabonomics was employed to analyze the serum metabolic features of DS deviated from CKS rats.PCA analysis and orthogonal partial least squares discriminant analysis(OPLS-DA)were utilized to explore the effect of DS on endogenous metabolites of rats,characterize the biomarkers,the relevant pathways and the underlying mechanism involved in DS against CKS.Results The pharmacodynamic results demonstrated that DS possessed beneficial activities in treating CKS.A total of 16 serum metabolites were selected as the potential biomarkers related to the development of CKS,12 out of them including LTyrosine,L-Tryptophan,L-Phenylalanine,isoleucine,betaine,pantothenic acid,etc.,were significantly regulated by DS.Fourteen metabolic pathways including amino acid metabolism,glycerophospholipid metabolism,pantothenate and CoA biosynthesis,etc.,were recognized to be the most relevant to efficacy of DS against CKS.Conclusion The obtained results showed that the inhibitory effect of DS on CKS may involve regulating levels of endogenous metabolites via multiple pathways,to restore the normal metabolic activity.
作者
赖丽嫦
陈丰连
王术玲
曹骋
LAI Lichang;CHEN Fenglian;WANG Shuling;CAO Cheng(School of Pharmaceutical Science,Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;Guangzhou Kingmed Diagnostics Central Co Ltd,Guangzhou 510320 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2020年第8期950-959,共10页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家中医药管理局项目(201507002)
广东省科技计划项目(2015B090901033)。
