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中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (8): 876-880.

• 研究原著 • 上一篇    下一篇

中药962对神经细胞内钙升高的血清药理学研究

熊杰, 成亮, 张丽1, 李林1   

  1. 首都医科大学化学生物学与药学院药理室, 北京 100054;
    1首都医科大学北京宣武医院老年医疗研究中心药理室, 北京 100053
  • 收稿日期:2005-06-01 修回日期:2005-06-22 发布日期:2020-11-22
  • 通讯作者: 熊杰,女,英国伯明翰大学博士后,讲师,研究方向:神经药理。Tel:010-63051453 E-mail:xiongjiejie2003@sohu.com
  • 基金资助:
    国家863计划课题(No2004AA2Z3815);2004年度留学回国人员科技活动择优资助项目

Serum pharmacology of Chinese herb complex 962 on increased intracellular calcium

XIONG Jie, CHENG Liang, ZHANG Li1, LI Lin1   

  1. Department of Pharmacology, School of Chemical Biology and Pharmacal Science, Capital University of Medical Sciences, Beijing 100054, China;
    1Department of Pharmacology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053, China
  • Received:2005-06-01 Revised:2005-06-22 Published:2020-11-22

摘要: 目的: 探讨中药复方962的小鼠血清制品(含药血清)对线粒体损伤造成的神经细胞内游离钙升高的影响及其作用机制。方法: 用3-nitropropionicacid(3-NPA)和1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)造成胎鼠神经细胞内钙升高模型。用Fura-2AM作细胞内钙的荧光指示剂,观察中药复方962的含药血清对神经细胞内游离钙升高的抑制作用,同时利用内钙释放剂Thapsigargin、外源性谷氨酸和KCl作工具药,对含药血清的作用环节进行分析。结果: 不同剂量和不同处理时间的含药(962)血清对MPTP和3-NPA造成的神经细胞内钙增高都有明显的抑制作用,而且表现出良好的量效关系。在MPTP和3-NPA模型中,作用最强的分别是给药3d和14d得到的血清。含药血清能抑制谷氨酸和KCl引起的细胞内钙增高,大剂量下对Thapsigargin造成的内钙升高也有抑制作用。结论: 中药复方962对MPTP和3-NPA造成的神经细胞内钙增高有抑制作用,在两种模型中起效的主要成分份不同,可能分别为原药早期代谢产物和后期代谢产物活性因子。作用机制主要是抑制细胞外钙内流,大剂量对细胞内钙库的释放也有影响。

关键词: 血清药理学, 细胞内钙, 3-NPA, MPTP, Fura-2 AM

Abstract: AIM: To investigate the effects and mechanisms of 962-contained mice-serum on intracellular calcium ([Ca2+] i) caused by injury of mitochondria. METHODS:MPTP and 3-NPA were used as mitochondrial inhibitors to trigger the increase of [Ca2+] i.Using Fura-2 AM as the fluorescent indicator of [Ca2+] i, the inhibit effects of 962-contained serum were detected, and the mechanisms were analyzed by adding Thapsigargin, glutamine or KCl to the neurons.RESULTS: 962-contained mice-serum showed significant inhibitive effects on [Ca2+] i increasing in a dose-dependent manner.For MPTP, the strongest inhibition was obtained by serum from mice that administrated 962 for 3 days (d-3 serum), while for 3-NPA it was the d-14 serum that showed the strongest effect.The mechanical study showed that the d-3 serum inhibited the increasing of [Ca2+] i caused by glutamine or KCl, and the effect of Thapsigargin was also found at a higher dosage.CONCLUSION: 962-contained serum shows inhibitory effects on [Ca2+] i increasing caused by MPTP or 3-NPA, in which the primary or the secondary metabolites of 962 played the key role.The mechanical analysis shows that this protective effect on the increasing of [Ca2+] i is mainly mediated by inhibiting the influx of calcium from outside.

Key words: serum pharmacology, intracellular calcium, 3-NPA, MPTP, Fura-2 AM

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