中国药理学通报2025，Vol.41Issue(7)：1318-1324,7.DOI:10.12360/CPB202411049
肥胖小鼠肾脏Oatp4c1-P-gp跨膜转运系统对地高辛药代动力学的影响
Influence of Oatp4c1-P-gp transmembrane transport system in the kidneys of obese mice on the pharmacokinetics of digoxin
摘要
Abstract
Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.关键词
高脂饮食/肥胖小鼠/肾脏/Oatp4c1-P-gp/地高辛/清除率Key words
high-fat diet/obese mice/kidney/Oatp4c1-P-gp/digoxin/clearance rate分类
医药卫生引用本文复制引用
门静文,孙璐,岳浩然,段兆月,侯慧楠,桂婷,辛军红,盖秩舶..肥胖小鼠肾脏Oatp4c1-P-gp跨膜转运系统对地高辛药代动力学的影响[J].中国药理学通报,2025,41(7):1318-1324,7.基金项目
山东省自然科学基金资助项目(No ZR2023QH014) （No ZR2023QH014）
