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

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (3): 275-280.

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

杨志勇, 刘国卿, 黄文龙¹

中国药科大学药理教研室;¹药物研究中心, 南京210009, 江苏

收稿日期:2003-08-29 接受日期:2003-11-07 出版日期:2004-03-26 发布日期:2020-11-21
通讯作者: 戴德哉, 教授, 博导, 研究方向:心血管药理学。Tel:025-3271270 　Fax:025-3302827 　E-mail:dezaidai@vip.sina.com
基金资助:
国家自然科学基金重点项目(№30230170);国家自然科学基金项目(№30171078)

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

YANG Zhi-Yong, LIU Guo-Qing, HUANG Wen-Long¹

Department of Pharmacology, ¹Center of Drug Research, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2003-08-29 Accepted:2003-11-07 Online:2004-03-26 Published:2020-11-21
Contact: LIU Guo-Qing, male, doctor director, prof essor, engaged in nerve and cerebral vessels pharmacology.Tel:025-3271340 　E-mail:lugq@cpu.edu.cn
About author:YANG ZhiYong, male, PhD candidate, engaged in nerve and cerebral vessels pharmacology.Tel:025-3245740 　E-mail:yzy_sec@sina.com

摘要/Abstract

摘要： 目的:观察新合成四氢异喹啉衍生物H108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H108 对K562/ADR 细胞株及大鼠脑微血管内皮细胞(RBMECs) 内罗丹明123(Rh123) 积聚的影响, 考察H108 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(Na₂S₂O₄) 建立缺血缺氧损伤模型, 过氧化氢(H₂O₂) 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H108 对三种PC12 损伤细胞存活率的影响。结果:H108 浓度依赖性地增加K562/ADR 及RBMECs 细胞中Rh123 的累积浓度。并可明显对抗Na₂S₂O₄及SNP诱导的PC12 细胞损伤, 增加细胞存活率。结论:H108 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-gp 逆转剂。

关键词: 四氢异喹啉, P-糖蛋白, 多药耐药, K562/ADR, 大鼠脑微血管内皮细胞, PC12 细胞

Abstract: 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 (Na₂S₂O₄), sodium nitroprusside (SNP) and hydrogen peroxide (H₂O₂).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 Na₂S₂O₄ 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 Pgp of BBB.

Key words: tetrahydroisoquinoline, P-glycoprotein, multidrug resistance, K562/ADR, rat brain microvessel endothelial cells, PC12 cells

中图分类号:

R965.1

杨志勇, 刘国卿, 黄文龙. 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[J]. 中国临床药理学与治疗学, 2004, 9(3): 275-280.

YANG Zhi-Yong, LIU Guo-Qing, HUANG Wen-Long¹. Effects of novel tetrahydroisoquinoline derivative-H108 on activity of P-glycoprote in virto and injury of PC12 cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 275-280.

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