基于UHPLC-Q-TOF-MS/MS技术揭示丹参水提液在急性血瘀证大鼠中的成分动态分布特征OA
Elucidating Dynamic Distribution of Components in Salvia miltiorrhiza Extract in Rats with Acute Blood Stasis Syndrome by UHPLC-Q-TOF-MS/MS
目的 基于超高效液相色谱(Ultra high performance liquid chromatography,UHPLC)-四极杆(Quadrupole,Q)-飞行时间(Time of flight,TOF)-质谱(Mass spectrometry,MS)/MS联用技术,系统研究丹参水提液在急性血瘀证模型大鼠体内的动态分布规律,反映其多成分、多器官协同调控的特点,为丹参活血化瘀药效物质基础研究提供依据.方法 15只SD大鼠随机分为空白组(生理盐水)、模型组(生理盐水)和丹参水提液组(5.4 g·kg-1),其中模型组及给药组连续灌胃10 天后进行急性血瘀证造模.采用UHPLC-Q-TOF-MS/MS技术,正、负离子模式下检测丹参水提液及末次给药后0.25、0.5、1、2、4 h的大鼠血浆及各组织(心、肝、脾、肺、肾、结肠)、排泄物(尿液、粪便)样本,通过峰面积相对定量法解析原型成分的分布特征.结果 在丹参水提液中共鉴定到133个成分.在给药后不同时间点血浆中检出原型成分40个,组织分布呈现显著数量差异性(结肠54个>肺48个>肝脏21个>肾脏19个>脾11个>心脏10个),排泄物中尿液、粪便分别检出48和65个成分.丹参水提液在血瘀证大鼠体内的成分以二萜类(如丹参酮ⅡA)及酚酸类(如丹酚酸B)成分为主,给药后1 h血浆中总成分含量达峰;组织分布总暴露量同样存在差异性(结肠>肺>肾脏>肝脏>心脏>脾),首次发现水苏糖在血浆及结肠有显著分布;粪便的总成分检出量和相对丰度显著高于尿液.结论 本研究首次系统揭示了丹参水提液在病理模型下的体内分布规律,构建了"成分-多组织响应"分布可视化图谱;化合物的动态成分分布表征特点表明,除二萜类及酚酸类外,水苏糖在丹参通过多系统互作重塑机体稳态的整体功效中也具有重要作用.
Objective To systematically investigate the dynamic distribution of Salvia miltiorrhiza(SM)extract in acute blood stasis model rats by UHPLC-Q-TOF-MS/MS,and explore its multi-component and multi-organ synergistic characteristics,thereby providing a scientific data for the pharmacodynamic material foundation elucidation of its blood-activating and stasis-resolving effects.Methods Fifteen Sprague-Dawley rats were randomly divided into blank group,model group and SM extract group.Rats in the model group and SM extract group were induced as acute blood stasis syndrome,and rats in the SM extract group were given SM extract at a dose of 5.4 g·kg-1 for 10 consecutive days.Biological samples from the SM extract group were analyzed by UHPLC-Q-TOF-MS/MS in both positive and negative ionization modes.Plasma was collected at different timepoints including 0.25,0.5,1,2,and 4 h on day 11.Organs likes heart,liver,spleen,lung,kidney,and colon,and excreta like urine and feces were also collected on day 11.The contents of prototype components were determined and compared among groups using peak area-based relative quantification method.Results A total of 133 compounds were identified in the SM extract.40 prototype components were detected in plasma at different timepoints.Tissue distribution characteristic was observed as colon(54)>lung(48)>liver(21)>kidney(19)>spleen(11)>heart(10).In addition,48 and 65 prototypes were detected in urine and feces,respectively.Diterpenoids such as tanshinone Ⅱ A,and phenolic acids such as salvianolic acid B were the predominant constituents in the blood stasis model rats,which plasma concentration peaked at 1 h post administration.The prototype exposure varied significantly among the detected organs:colon>lung>kidney>liver>heart>spleen.Notably,stachyose was found in the plasma and the colon tissue for the first time.The prototype compounds showed higher quantities and contents in the feces than those in the urine.Conclusion This study systematically firstly reveals the in vivo distribution profile of SM extract in a pathological model,and establish a visual spectrum of"component-multi-tissue response".The dynamic distribution patterns of the compounds emphasized the important role of stachyose in multi-system interactions to remodel organismal homeostasis when Salvia miltiorrhiza treating acute blood stasis syndrome,as well as the diterpenoids and phenolic acids.
杨丽媛;唐婷婷;王超;李娟;高洁;庞涛;张凤;陈万生
上海中医药大学中药研究所 上海 201203海军军医大学第二附属医院药剂科 上海 200003上海中医药大学中药研究所 上海 201203安徽中医药大学药学院 合肥 230012海军军医大学第二附属医院药剂科 上海 200003海军军医大学第二附属医院药剂科 上海 200003上海中医药大学中药研究所 上海 201203||海军军医大学第二附属医院药剂科 上海 200003||安徽中医药大学药学院 合肥 230012上海中医药大学中药研究所 上海 201203||海军军医大学第二附属医院药剂科 上海 200003
医药卫生
丹参水提液超高效液相色谱-四极杆-飞行时间质谱联用技术急性血瘀证成分动态分布
Salvia Miltiorrhiza extractUHPLC-Q-TOF-MS/MSAcute blood stasis syndromeDynamic component distribution
《世界科学技术-中医药现代化》 2026 (6)
1868-1882,15
科技部重点研发计划(2022YFC3501700):临床证据导向的丹参、党参"功效-物质"全景解析及深度研发,负责人:陈万生上海市科学技术委员会项目(22S21901900):治疗心律失常制剂益心饮的临床前研究,负责人:张凤上海中医药大学有组织科研重点专项(2023YZZ02):基于物质-功效解析的气血理论科学阐释,负责人:陈万生.
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