中药962对神经细胞内钙升高的血清药理学研究

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

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

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

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/Abstract

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

中图分类号:

R285

熊杰, 成亮, 张丽, 李林. 中药962对神经细胞内钙升高的血清药理学研究[J]. 中国临床药理学与治疗学, 2005, 10(8): 876-880.

XIONG Jie, CHENG Liang, ZHANG Li, LI Lin. Serum pharmacology of Chinese herb complex 962 on increased intracellular calcium[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(8): 876-880.

参考文献

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