天然产物研究与开发 ›› 2019, Vol. 31 ›› Issue (3): 512-516.doi: 10.16333/j.1001-6880.2019.3.023

• 开发研究 • 上一篇    下一篇

NR2B与钩藤碱抑制甲基苯丙胺依赖斑马鱼CPP的关系研究

朱晨1,刘伟1,罗超华1,陈志杰1,周玉婷1,霍楚莹1,李璟2,莫志贤1*   

  1. 1南方医科大学中医药学院;2南方医科大学中心实验室,广州 510515

  • 出版日期:2019-04-02 发布日期:2019-04-02
  • 基金资助:

    国家自然科学基金(81673628,81573706);广州市科技计划(201707010287)

Rhynchophylline reverses methamphetamine-induced CPP by regulating the expression of NR2B in zebrafish

ZHU Chen1,LIU Wei1,LUO Chao-hua1,CHEN Zhi-jie1,ZHOU Yu-ying1,HUO Chu-ying1,LI Jing2,MO Zhi-xian1*   

  1. 1School of Traditional Chinese Medicine,Southern Medical University; 2Central Laboratory,Southern Medical University,Guangzhou 510515,China
  • Online:2019-04-02 Published:2019-04-02

摘要: 研究N-甲基-D-天冬氨酸受体2B亚基(NR2B) 与钩藤碱抑制甲基苯丙胺依赖斑马鱼条件性位置偏爱(condition place preference,CPP)作用的关系。斑马鱼分为5组:空白组、模型组(甲基苯丙胺40 mg/kg)、钩藤碱低剂量组(40 mg/kg)、钩藤碱高剂量组(80 mg/kg)、氯胺酮组(150 mg/kg)。腹腔注射甲基苯丙胺后,进行斑马鱼条件性位置偏爱训练,建立斑马鱼甲基苯丙胺CPP依赖模型,分析各组斑马鱼在CPP箱中的活动,以及各组斑马鱼脑内NR2B的表达情况。腹腔注射甲基苯丙胺40 mg/kg后,甲基苯丙胺依赖斑马鱼CPP模型成功建立。与空白组相比,模型组斑马鱼在伴药箱中的时间明显增加;与模型组相比,钩藤碱高剂量组斑马鱼在伴药箱中的时间明显减少。与空白组相比,模型组斑马鱼脑内NR2B阳性细胞数明显增加;给予钩藤碱干预后,斑马鱼脑内NR2B阳性细胞数明显减少。与空白组比较,模型组斑马鱼脑内NR2B蛋白表达明显增强,而给予钩藤碱干预后,NR2B蛋白表达减弱。钩藤碱可抑制甲基苯丙胺诱导的斑马鱼CPP效应,其机制与抑制NR2B的表达有关。

关键词: 钩藤碱, 甲基苯丙胺, 条件性位置偏爱, N-甲基-D-天冬氨酸受体2B亚基, 斑马鱼

Abstract: To investigate the effect of rhynchophylline on the expression of NMDA receptor 2B subunit (NR2B) in methamphetamine-induced condition place preference (CPP) in zebrafish.Zebrafish were randomly divided into control group,model group (methamphetamine 40 mg/kg),ketamine (150 mg/kg),rhynchophylline (40 mg/kg) group and rhynchophylline (80 mg/kg) group.After intraperitoneal injection of methamphetamine,zebrafish CPP training was carried out,and the methamphetamine CPP-dependent zebrafish model was established.The activity of zebrafish in CPP compartment and the expression of NR2B in zebrafish brain were analyzed.Compared with control group,the residence time of model group in drug pair compartment was significantly increased.Compared with model group,the residence time of rhynchophylline (80 mg/kg) group in drug pair compartment was significantly decreased.The result of immunohistochemistry showed that methamphetamine (40 mg/kg) increased the number of NR2B positive cells in zebrafish brain.However,treatment with ketamine (150 mg/kg),rhynchophylline (40,80 mg/kg) reduced the number of NR2B positive cells in zebrafish brain.Western blot indicated the expression of NR2B of model group increased significantly.The zebrafish in ketamine (150 mg/kg) and rhynchophylline (80 mg/kg) group had less NR2B expression.NR2B plays a key role in the methamphetamine-induced CPP in zebrafish.Rhynchophylline reverses methamphetamine-induced CPP by regulating the expression of NR2B in zebrafish.

Key words: rhynchophylline, methamphetamine, condition place preference, NR2B, zebrafish

中图分类号: 

R285