中药962对神经细胞内钙升高的血清药理学研究  

Serum pharmacology of Chinese herb complex 962 on increased intracellular calcium

作　　者：熊杰[1] 成亮[1] 张丽[2] 李林[2] 

机构地区：[1]首都医科大学化学生物学与药学院药理室,北京100054 [2]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

出　　处：《中国临床药理学与治疗学》2005年第8期876-880,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家863计划课题(№2004AA2Z3815);2004年度留学回国人员科技活动择优资助项目。

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-tetrahydro-pyridine(MPTP)造成胎鼠神经细胞内钙升高模型。用Fura-2/AM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。AIM： To investigate the effects and mechanisms of 962-contained mice-serum on intraeellular calcium （ [ Ca^2＋ ]i ） caused by injury of mitochondfia. METHODS： MPTP anti 3-NPA were used as mitochondrial inhibitors to trigger the increase of [ Ca^2＋]i. Using Fura-2/AM as the fluorescent indicator of [Ca^2＋ ]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 [Ca^2＋]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 [ Ca^2＋ ]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 [ Ca^2＋ ]i increasing caused bv 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 [ Ca^2＋ ]i is mainly mediated by inhibiting the influx of calcium from outside.

关 键 词：血清药理学 细胞内钙 3-NPA MPTP FURA-2/AM 

分 类 号：R285[医药卫生—中药学]