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作 者:宋金洋 逯文翰 刘蓬蓬[3] 郭晓宇 SONG Jinyang;LU Wenhan;LIU Pengpeng;GUO Xiaoyu(Peking University Health Science Center,Beijing 100191,China;The High School Affiliated to Renmin University of China,Beijing 100097,China;Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)
机构地区:[1]北京大学医学部,北京100191 [2]中国人民大学附属中学,北京100097 [3]辽宁中医药大学,辽宁沈阳110847
出 处:《辽宁中医药大学学报》2025年第3期21-27,共7页Journal of Liaoning University of Traditional Chinese Medicine
基 金:国家自然科学基金(81974551,81573684)。
摘 要:目的阐明肠道菌群变化对大鼠体内三七-红花有效组分(CNS)主要药效成分的药代动力学影响。方法采用亚胺培南/西司他丁钠腹腔注射1周,诱导拟无菌大鼠模型。正常大鼠和拟无菌大鼠均灌胃CNS后,在不同时间点采集血浆,使用液相色谱串联质谱法(LC-MS/MS)测定给药后血浆中羟基红花黄色素A(HSYA),三七皂苷R1,人参皂苷Rb1、Rg1、Rd和Re的浓度,并使用DAS 3.0软件计算药代动力学参数。结果通过前期已建立的大体积进样体系,检测CNS中6个主要药效成分的血药浓度。结果显示,与正常大鼠相比,拟无菌大鼠体内药-时曲线下面积(AUC0-t)和最大血药浓度值(Cmax)均升高,其中6个主要药效成分的Cmax差异均具有统计学意义。结论抑制肠道菌群后,会导致CNS中主要药效成分的体内暴露量增加。Objective To elucidate the pharmacokinetic effects of gut microbiota on the main active components of the combination of Sanqi(Notoginseng Radix Et Rhizoma)and Honghua(Carthami Flos)(CNS)in rats.Methods Intraperitoneal injection of imipenem/cilastatin sodium for one week to induce a pseudo sterile rat model.After oral administration of CNS,plasma was collected at different time points in both normal and pseudo sterile rats.The concentrations of hydroxysafflower yellow A(HSYA),notoginsenoside R1,ginsenoside Rb1,ginsenoside Rg1,ginsenoside Rd,and ginsenoside Re in the plasma were measured by liquid chromatography-mass spectrometry/mass spectrometry(LC-MS/MS)after administration,and pharmacokinetic parameters were calculated using DAS 3.0 software.Results The plasma concentrations of six main active ingredients in CNS were detected through the established large volume direct injection system.The results showed that compared with normal rats,the area under the drug time curve(AUC0-t)and peak concentration(Cmax)of pseudo sterile rats increased in vivo,and the Cmax of the six main active ingredients showed significant differences.Conclusion Inhibiting gut microbiota can lead to increase in vivo exposure of the main active ingredients in CNS.
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