四氢帕马丁在MDCK-MDR1细胞系中的跨膜转运机制

目的:研究四氢帕马丁(tetrahydropalmatine,THP)在MDCK-MDR1单层细胞模型中的跨膜转运机制。方法:利用MDCK-MDR1单层细胞模型研究在有或无P-糖蛋白(P-gp)专属抑制剂维拉帕米时,THP双向转运特性,同时考察了温度、浓度对THP吸收的影响。采用HPLC法测定THP的含量,计算其表观渗透系数(Papp)。结果:当加入100μg/ml维拉帕米时,细胞单层顶端(apical,A)→基底端(basolateral,B)的Papp(A→B)增加,而B→A的Papp(B→A)显著降低。不加维拉帕米时外排率值为5.5,添加维拉帕米时外排率值为3.9。结论:THP在MDCK-MDR1单层细胞模型中的转运受到P-gp的外排作用,THP可能是P-gp的作用底物。THP跨MDCK-MDR1单层细胞转运具有温度依赖性和浓度饱和性。

Transmembrane transport mechanism of tetrahydropalmatine in MDCK-MDR1 cell line

Objective: To investigate the transmembrane transport mechanism of tetrahydropalmatine(THP) in MDCK-MDR1 cell line.Methods: The bi-directional transport characteristics of THP with or without verapamil,which was a specific inhibitor of P-glycoprotein(P-gp),was observed in MDCK-MDR1 cell line.The effects of temperature and concentration of THP on the absorption of THP were also investigated.The concentration of THP was determined by HPLC method and the apparent permeability coefficient(Papp) of THP was calculated.Results: In the presence of 100 μg/ml verapamil,the Pappof THP from apices of cell monolayers(A) to bases of cell monolayers(B) was increased,while that from B to A was significantly reduced.In the absence of verapamil,the efflux rate value was 5.5,which was reduced to 3.9 in the presence of verapamil.Conclusion: The transport of THP in MDCK-MDR1 cell monolayers is effluxed by P-gp.THP may be a substrate of P-gp.The transmembrane transport of THP in MDCK-MDR1 cell monolayers is found to be temperature dependent and there is concentration saturation.