摘要
目的:基于超高效液相色谱-四极杆-静电场轨道阱-线性离子阱质谱法(UPLC-Orbitrap Fusion Lumos Tribrid-MS),测定口服给药后不同时间点地榆皂苷Ⅰ的血药浓度,对比分析其在正常大鼠与急性肾损伤大鼠体内的药代动力学特征。方法:将48只雄性SD大鼠随机分为正常组和模型组,模型组腹腔注射顺铂(10 mg·kg^(-1))建立急性肾损伤模型,正常组给予等体积生理盐水。造模成功后,正常组及模型组大鼠随机分为正常低、中、高剂量组(2.5、5、7.5 mg·kg^(-1))和模型低、中、高剂量组(2.5、5、7.5 mg·kg^(-1)),每组6只,分别灌胃相应剂量的地榆皂苷Ⅰ后收集不同时间点的血浆,采用UPLC-Orbitrap Fusion Lumos Tribrid-MS测定大鼠血浆中地榆皂苷Ⅰ的质量浓度,绘制药-时曲线,利用Kinetica 5.1软件计算药代动力学参数,以SPSS 22.0进行独立样本t检验比较不同给药组间药代动力学参数的差异。结果:药代动力学结果显示,灌胃不同剂量的地榆皂苷Ⅰ后,其浓度均表现为先增大后减小,且均在0.5 h左右达到最大血药浓度;正常大鼠和模型大鼠药时曲线下面积(AUC_(0-t))、平均滞留时间(MRT_(0-t))随给药剂量增加而增多,清除率(CL)随给药剂量增加而减少。与正常组比较,不同给药剂量下模型组大鼠的AUC_(0-t)均显著增加(P<0.01)、达峰浓度(C_(max))均升高、CL均降低,表明动物的生理状态会影响地榆皂苷Ⅰ在体内的吸收与消除。结论:地榆皂苷Ⅰ在正常大鼠体内和急性肾损伤模型大鼠体内药代动力学特征存在较大差异,可能为病理状态下体内环境变化,进而导致吸收和代谢过程发生变化。
Objective:Based on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital traplinear ion-trap mass spectrometry(UPLC-Orbitrap Fusion Lumos Tribrid-MS),the plasma concentration of ziyuglycosideⅠwas determined at different time points after oral administration,and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared.Methods:Rats were randomly divided into normal group and model group,the model group received intraperitoneal cisplatin(10 mg·kg^(-1))to establish the acute kidney injury model,the normal group was given the same volume of saline.After successful modeling,rats in the normal and model groups were randomly divided into the normal low,medium and high dose groups(2.5,5,7.5 mg·kg^(-1))and the model low,medium and high dose groups(2.5,5,7.5 mg·kg^(-1)),6 rats in each group,and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycosideⅠ.Then,the concentration of ziyuglycosideⅠin rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS,and the drug-time curve was poltted.The pharmacokinetic parameters were calculated by Kinetica 5.1 software,and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0.Results:The pharmacokinetic results showed that after receiving the different doses of ziyuglycosideⅠ,its concentration increased first and then decreased,and all of them reached the maximum plasma concentration at about 0.5 h.The area under the curve(AUC_(0-t))and mean retention time(MRT_(0-t))of normal and model rats increased with the increased dose,and the clearance(CL)decreased with the increasing dose.Compared with the normal group,the AUC_(0-t) was significantly increased(P<0.01),peak concentration(C_(max))and CL decreased in model rats at different doses,indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycosideⅠin vivo.Conclusion:The pharmacokinetic characteristics of ziyuglycosideⅠare quite different in normal rats and acute kidney injury model rats,which may be due to the change of the body environment in the pathological state,then lead to changes in absorption and metabolic processes.
作者
张允惠
刘艳丽
许琼明
孙淑仃
朱泓锦
赵迪
冯素香
ZHANG Yunhui;LIU Yanli;XU Qiongming;SUN Shuding;ZHU Hongjin;ZHAO Di;FENG Suxiang(Henan University of Chinese Medicine,Zhengzhou 450046,China;Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan province&Education Ministry of P.R.China,Zhengzhou 450046,China;Soochow University,Suzhou 215000,China)
出处
《中国实验方剂学杂志》
北大核心
2025年第5期203-210,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
河南省科技攻关项目(202102311095)。
