甘松新酮对缺糖缺氧损伤原代培养神经元的保护作用  

Nardosinone reduces neuronal injury induced by oxygen-glucose deprivation in primary cortical cultures

作　　者：李玮[1] 石晋丽[1] 李琴[1] 段惠惠[1] 唐民科[1] 

机构地区：[1]北京中医药大学中药药理系,北京100102

出　　处：《药学学报》2013年第9期1422-1429,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30772763);教育部新世纪优秀人才支持计划(2010)

摘　　要：观察甘松新酮对缺糖缺氧损伤原代培养神经元的保护作用。采用孕14天小鼠胚胎皮层制备原代培养神经元;MTT法确定甘松新酮对原代培养神经细胞的安全剂量,并观察其对缺糖缺氧神经元的保护作用;采用Western blotting法观察药物对缺糖缺氧损伤神经元以及正常培养神经元蛋白激酶A(PKA)和细胞外信号调节激酶(ERK)通路关键蛋白表达的影响。结果显示,甘松新酮(50和100μmol·L-1)能够增加缺糖缺氧损伤神经元的存活率(P<0.01,与OGD组比较);同时,能增加缺糖缺氧神经元PKA、小分子G蛋白Ras的相关蛋白1(Rap1)、丝裂原激活的蛋白激酶的激酶1(MEK1)及磷酸化的ERK1/2(p-ERK1/2)的表达,且此作用呈剂量依赖趋势。对正常培养神经元研究结果显示,甘松新酮(50、100和200μmol·L-1)也能增加其PKA、Rap1、MEK1及p-ERK1/2的表达(P<0.01)。以上结果表明,甘松新酮对缺糖缺氧损伤的原代培养神经元有明确保护作用,该作用可能与药物激活PKA和ERK通路有关。The aim of the study is to investigate the effect of nardosinone （Nar） on neuronal injury induced by oxygen-glucose deprivation （OGD） in primary cortical cultures isolated from embryos at gestational day 14. MTT method was used to determine the dosage regimen of Nat in primary neuronal cultures and observe the influence of Nar on the neurons suffering OGD; Western blotting analysis was used to detect expressions of protein kinase A （PKA）, Ras related protein 1 （Rap1）, mitogen-activated protein kinase kinase 1 （MEK1） and phospho-extracellular signal-regulated kinase 1/2 （p-ERK1/2） of OGD-injured or uninjured primary cultured neurons after Nat treatment. Results showed that Nar （50 and 100 μmol·L^-1） improved the cell viability during OGD damage （P 〈 0.01） and increased the expression of PKA, Rapl, MEK1 and p-ERK1/2 in injured neurons. Additionally, elevations of PKA, Rap l, MEK1 and p-ERK1/2 in uninjured neurons were caused by Nat （50, 100 and 200 μmol·L^-1） with a dose-dependent tenclency as well （P 〈 0.01）. In conclusion, Nat could protect against the neuronal injury exposed to OGD, which may be relevant to the promotion of PICA and ERK signaling pathway.

关 键 词：甘松新酮 原代培养神经元 缺糖缺氧 PKA ERK 

分 类 号：R963[医药卫生—微生物与生化药学]