一种新四氢异喹啉类化合物H108体外抑制P-糖蛋白功能及对PC12细胞损伤的保护作用(英文)

Effects of novel tetrahydroisoquinoline derivative-H108 on activity of P-glycoprote in virto and injury of PC12 cells

目的 :观察新合成四氢异喹啉衍生物H10 8抑制P 糖蛋白 (P gp)功能及对PC12细胞损伤的保护作用。方法 :测定H10 8对K5 6 2 ADR细胞株及大鼠脑微血管内皮细胞 (RBMECs)内罗丹明 12 3(Rh12 3)积聚的影响 ,考察H10 8逆转P gp介导的多药耐药性及对血脑屏障上P gp药物外排功能的影响。以连二亚硫酸钠 (Na2 S2 O4)建立缺血缺氧损伤模型 ,过氧化氢 (H2 O2 )建立氧化应激损伤模型 ,硝普钠 (SNP)建立NO损伤模型 ,MTT法测定H10 8对三种PC12损伤细胞存活率的影响。结果 :H10 8浓度依赖性地增加K5 6 2 ADR及RBMECs细胞中Rh12 3的累积浓度。并可明显对抗Na2 S2 O4及SNP诱导的PC12细胞损伤 ,增加细胞存活率。结论 :H10 8具有一定的P gp逆转作 ,并可能具有一定的神经保护作用。其有可能成为一种新型、高效 ,特别是用于促进血脑屏障上药物转运的P

AIM: To observe the effects of H108, a novel tetrahydroisoquinoline derivative on the drug efflux activity of P glycoprotein (P gp) on K562/ADR and rat brain microvessel endothelial cells (RBMECs), and the protective effects on the injury of PC12 cells. METHODS: Fluorescence substrate of P gp rhodamine123 (Rh123) was used to examine the effects of H108 on the drug efflux activity of P gp on K562/ADR and RBMECs. The viability of PC12 cells was studied by MTT assay to assess the protective effect of H108 on the injury of PC12 cells that were induced by sodium dithionite (Na 2S 2O 4), sodium nitroprusside (SNP) and hydrogen peroxide (H 2O 2). RESULTS: H108 increased the intracellular accumulation of Rh123 in a dose dependent manner in RBMECs and K562/ADR.The viability rate of PC12 cells injuried by SNP and Na 2S 2O 4 increased significantly when pretreated with H108. CONCLUSION: H108 has relatively potent P gp reversal activity, and exhibits potential protective effects on neurons. It can be developed as a novel and potent P gp reverser, particularly acting on P gp of BBB.