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目的:寻找新型有效的血脑屏障P-糖蛋白逆转剂。方法:通过测定各化合物对牛脑微血管内皮细胞内罗丹明123积累的影响来考查它们对P-糖蛋白的功能性作用,以此筛选血脑屏障上的P-糖蛋白逆转剂。结果:各化合物浓度依赖性地增加胞内Rh123的累积浓度,作用强弱顺序为:环孢素A(CsA)>粉防己碱(Tet)>长春新碱(VCR)≈氟桂利嗪(Flu)>延胡索乙素(dl-THP)>蝙蝠葛碱(DRC)>阿齐霉素(Azi)>维拉帕米(Ver)≈小檗胺(BBM)>蝙蝠葛苏林碱(DRS)>小檗碱(BBR)>阿霉素(Dox)>左旋四氢巴马汀(l-THP)>川芎嗪(TMP)。其中CsA、Tet、Ver、Flu、Azi和dl-THP对胞内罗丹明123的累积的影响是可逆的。结论:多种中药单体,如某些异喹啉类生物碱能逆转血脑屏障上P-糖蛋白的功能,而不使血脑屏障上P-糖蛋白的固有水平发生永久性改变。
Objective: To find a new and effective blood-brain barrier P-glycoprotein reversal agent. METHODS: The effect of each compound on the accumulation of rhodamine 123 in bovine brain microvascular endothelial cells was determined by examining their functional effects on P-glycoprotein, and the P-glycoprotein reversal agent on the blood-brain barrier was screened. RESULTS: Each compound increased the concentration of intracellular Rh123 in a concentration-dependent manner. The order of the effects was: cyclosporine A (CsA)> tetrandrine (Tet)> vincristine (VCR) and flunarizine (Flu) )> Tetrahydropalmatine (dl-THP)> Doric Alkaloid (DRC)> Azithromycin (Azi)> Verapamil (Ver) Beta-Butylamine (BBM)> Batsaurine (DRS)> Betapril Base (BBR)> Doxorubicin (Dox)> Levotetrahydropalmatine (l-THP)> Tetramethylpyrazine (TMP). Among them, the effects of CsA, Tet, Ver, Flu, Azi, and dl-THP on the accumulation of intracellular rhodamine 123 were reversible. CONCLUSIONS: A variety of TCM monomers, such as certain isoquinoline alkaloids, can reverse the function of the P-glycoprotein on the blood-brain barrier without permanently altering the inherent level of P-glycoprotein on the blood-brain barrier.