[关键词]
[摘要]
目的 研究川芎嗪在Caco-2细胞单层模型的转运特征以及对P-糖蛋白(P-gp)表达的影响。方法 MTT法确定川芎嗪对Caco-2细胞单层模型作用的安全浓度范围;以Caco-2细胞单层模型研究川芎嗪的双向转运机制,以表观渗透系数(Papp)为检测指标,考察时间、药物浓度以及P-gp抑制剂维拉帕米对川芎嗪转运的影响;Western blotting法检测川芎嗪对P-gp表达的影响。结果 从顶侧(AP)到底侧(BL)(AP→BL),川芎嗪的Papp>10?6 cm/s,表明其吸收性良好;川芎嗪的转运量与其浓度和时间呈正相关,且川芎嗪AP→BL的转运量明显大于BL→AP的转运量;川芎嗪不仅受到P-gp的外排作用,同时也抑制P-gp表达。结论 川芎嗪在Caco-2细胞模型的转运方式为被动转运,且受到P-gp的外排作用,并对P-gp的表达有抑制作用。
[Key word]
[Abstract]
Objective To investigate the transport characteristics of ligustrazine across Caco-2 cell monolayer and the effect on P-glycoprotein (P-gp) expression. Methods Safe concentration range of ligustrazine against Caco-2 cell monolayer model was selected by the MTT method. The mechanism of ligustrazine bidirectional transport was investigated by Caco-2 cell monolayer model. The influences of time, concentration, and P-gp inhibitor Verapamil on the transport of ligustrazine were studied using apparent permeability coefficient (Papp) as index. P-gp expression in Caco-2 cells was analyzed by the Western blotting method. Results The Papp of transport from apical (AP) side to basolateral (BL) side was over 10?6 cm/s, which showed a good absorption. In the Caco-2 cell model, the transport amount of ligustrazine was positively correlated with time and concentration, and the transport amount from AP side to BL side was higher than that from BL to AP. The absorption of ligustrazine was not only rejected by P-gp, but also the P-gp expression was inhibited by ligustrazine. Conclusion The transport of ligustrazine across Caco-2 cell monolayer model is deduced as passive transport, ligustrazine is rejected by P-gp, and there is an inhibition of ligustrazine on the expression of P-gp.
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[基金项目]
国家自然科学基金资助项目(81202636,81274176,30973933);浙江省自然科学基金资助项目(Z2101201,LR12H27001);浙江省科技厅项目(2011C23039);浙江省中医药重点学科(2012-XK-A06);浙江省卫生高层次创新人才培养项目