【作者】 廖晓欢； 王俊俊； 韩凤梅； 杜鹏； 陈勇；

【Author】 LIAO Xiao-huan,WANG Jun-jun,HAN Feng-mei,DU Peng and CHEN Yong~*(Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine,Hubei University,Wuhan 430062)

【机构】 湖北大学中药生物技术省重点实验室；

【摘要】 研究氢氯噻嗪(hydrochlorothiazide)在Caco-2细胞中的跨膜转运特征。采用体外培养的人小肠上皮细胞模型Caco-2对氢氯噻嗪的跨膜转运进行研究。考察了浓度、时间、P-糖蛋白(P-glyprotein,P-gp)抑制剂维拉帕米(verapamil)以及pH对氢氯噻嗪跨膜转运的影响。氢氯噻嗪双向转运的Papp比值即Papp B→A/PappA→B均大于1.5。在加入P-gp抑制剂维拉帕米后,氢氯噻嗪PappA→B极显著增大,Papp B→A降低,且Papp B→A/PappA→B从2.87下降到0.67,加入前后有极显著差异(P<0.01)。氢氯噻嗪的吸收转运随pH的降低而显著增加。氢氯噻嗪在Caco-2细胞模型中的吸收可能存在由载体介导的主动转运,同时它还受到p-糖蛋白的外排作用。更多还原

【Abstract】 To study the transport characteristics of hydrochlorothiazide in vitro.A human intestinal epithelial cell Caco -2 model in vitro cultured had been applied to study the transport characteristics of hydrochlorothiazide.The effects of hydrochlorothiazide concentrations,conveying times,P-glyprotein(P-gp) inhibitor verapamil and conveying Liq pHs on the transport of hydrochlorothiazide were investigated.In the Caco-2 monolayer model,the apparent permeability coefficients(Papp) of hydrochlorothiazide transport from Basolateral(B) to Apical(A) was larger than that of the opposite direction.In the presence of verapamil,a P-glycoprotein inhibitor,the ratio of Papp B→A and Papp A→B was significantlly decreased from 2.87 to 0.67(P<0.01).Meanwhile,the ratio of Papp B→A and Papp A→B in pH 6.0 was significantlly less than that in pH 7.4(ratio 0.38 versus 2.81,respectively,P<0.01).The absorption of hydrochlorothiazide in Caco-2 cell model should be an active transport mediated by transporter,along with excretion action mediated by P-glycoprotein.更多还原