摘要
目的本研究建立Caco-2单层细胞模型研究野鸦椿酸摄取和转运特性。方法采用超高效液相色谱-三重四极杆质谱联用仪(UPLC-TQ-MS)测定野鸦椿酸的含量,考察不同时间、温度对其摄取的影响,在此基础上考察不同浓度、P-gp抑制剂、螯合剂和pH对其双向转运的影响。结果在37℃条件下,野鸦椿酸在Caco-2细胞模型上180 min时的摄取量为(8.38±0.87)μg/mg。野鸦椿酸低、中、高浓度的表观渗透系数(Papp值)与浓度呈正相关,分别为(61.41±2.92)×10^(-4)、(146.90±14.91)×10^(-4)、(167.18±6.72)×10^(-4)cm/s,P-gp抑制剂和螯合剂对其Papp值无影响,弱酸性环境(pH=6.00)可明显提高其Papp值,其外排率(ER)介于0.8~1.4之间。结论在Caco-2细胞模型中野鸦椿酸跨膜渗透性良好,其主要吸收方式为被动扩散,不是P-gp的底物,且不存在细胞旁路转运。本研究可为含有野鸦椿酸的药物的体内肠道吸收提供实验依据。
Objective Explore euscaphic acid uptake and transport mechanisms in Caco-2 cells.Methods Ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry(UPLC-TQ-MS)was employed to determine the content of euscaphic acid.The effects of various times and temperatures on its uptake were investigated.On the basis of the result of uptake analyses,the effects of various concentrations,P-gp inhibitors,chelating agents,and pH values on its bidirectional transport were explored.Results Euscaphic acid uptake was(8.38±0.87)μg/mg for 180 min in Caco-2 cells at 37℃.The apparent permeability coefficient(Papp)values of euscaphic acid at low,medium,and high concentrations were(61.41±2.92)×10^(-4),(146.90±14.91)×10^(-4),and(167.18±6.72)×10^(-4)cm/s,respectively,which were positively correlated to the concentrations.P-gp inhibitors and chelating agents had no effect on Papp values.A weakly acidic environment(pH=6)significantly increased the Papp value,and the efflux rate ranged from 0.8 to 1.4.Conclusions Euscaphic acid has good transmembrane permeability in Caco-2 cells,and the uptake mode is mainly passive diffusion.It is not a substrate of P-gp and no cellular bypass transport exists.This study may provide an experimental basis for in vivo intestinal absorption of medicines containing euscaphic acid.
作者
王宁
谢莉
丁文欢
田莉
WANG Ning;XIE Li;DING Wenhuan;TIAN Li(College of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830011,China;Xinjiang Uygur Autonomous Region Institute of Pharmaceutical Inspection,Urumqi 830011.;Xinjiang Key Laboratory of Famous Medicine and Famous Prescription and Characteristic Formulae,Urumqi 830011)
出处
《中国比较医学杂志》
CAS
北大核心
2023年第9期1-7,共7页
Chinese Journal of Comparative Medicine
基金
国家自然科学基金项目(81860744)
新疆维吾尔自治区“十四五”重点学科中医学。
