摘要
inducing resuscitation with herbal aromatics is important to modulate the brain intake of drugs in traditional Chinese medicine,but limited information has been available on the mechanism of action.The MDCK-MDRl monolayer is an excellent in vitro cell model to use as a tool to study blood brain barrier（BBB） screening.In this study,we established MDCK-MDR1 cell line by stable transfection and investigated the effects of several important herbal aromatics on BBB permeability.The characterization experiment demonstrated the MDCK-MDRl used in this study was valid.In a transport study,we found several herbal aromatics increased the permeability of fluorescein isothiocyanate-labeled dextran 4kDa（FD4） and inhibited efflux of Rhodaminel23（Rhol23）.These results demonstrated that herbal aromatics enhanced the BBB permeation of drugs by both inhibition of P-gp and opening of the BBB tight junction,thus providing new insights for understanding the mechanisms of aromatic compounds＇ BBB permeability.
在中医理论体系中,芳香开窍类药物对于调节脑部的药物摄取具有重要的作用。对于此作用的分子机制研究目前仍然有限。MDCK-MDR1细胞是研究药物透过血脑屏障机制的一个理想体外模型,本文用稳定转染的方法建立了MDCK-MDR1细胞系并研究了几种重要的芳香药物对BBB透过性的作用。研究结果表明:我们发现芳香开窍化合物可以在MDCK-MDR1模型上增加FD4的透过性并减少Rho123的外排,说明这些化合物一方面可以打开细胞间的紧密联接,另一方面可以抑制P-gp的作用,从而影响药物吸收。此研究为阐明芳香化合物的作用机制提供了新的见解。
基金
Major New Medicine Project in Mega-projects of Science Research of China(Grant No.2009ZX09502-006)
National Natural Science Foundation of China(Grant No.20971008)
