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藁本内酯对低钾大鼠小脑颗粒神经元凋亡的保护作用
引用本文:李玲姣,王宇,王良芬等. 藁本内酯对低钾大鼠小脑颗粒神经元凋亡的保护作用[J]. 四川大学学报(医学版), 2015, 46(1): 42-46
作者姓名:李玲姣  王宇  王良芬等
作者单位:1.四川大学华西药学院 药理学系
摘    要:目的 探讨藁本内酯(ligustilide, LIG)对原代培养小脑颗粒神经元细胞(cerebellar granule neurons, CGN)低钾性凋亡的影响。方法 建立低钾诱导体外培养新生大鼠CGN凋亡模型,将CGN分为对照组、模型组、CGP54626+LIG组及LIG组,分别进行给药处理;采用噻唑兰 (MTT) 法检测各组细胞存活率,Western blot检测胰岛素样生长因子1(IGF-1)信号通路中主要效应分子IGF-1R、Akt、ERK1/2、CREB及caspase 3的蛋白表达水平。 结果 LIG(2.5~20 μmol/L) 可浓度依赖性抑制大鼠 CGN的低钾性凋亡、提高其存活率; 20 μmol/L LIG 可显著上调IGF-1R、Akt、ERK1/2 和CREB 的磷酸化水平,下调 cleaved-caspase 3 的表达水平;同时,LIG上述效应均可被γ-氨基丁酸代谢型受体(GABAB)的选择性拮抗剂 CGP54626 所阻断。结论 LIG 对低钾所致大鼠CGN凋亡有保护作用,其机制可能与激活GABAB受体及其下游的 IGF-1 信号通路有关。

关 键 词:藁本内酯 GABAB受体 IGF-1信号通路 小脑颗粒神经元

Protective Effect of Ligustilide against Low Potassium Induced Apoptosis in Cultured Rat Cerebellar Granule Neurons
LI Ling-jiao,WANG Yu,WANG Liang-Fen,et al. Protective Effect of Ligustilide against Low Potassium Induced Apoptosis in Cultured Rat Cerebellar Granule Neurons[J]. Journal of Sichuan University. Medical science edition, 2015, 46(1): 42-46
Authors:LI Ling-jiao  WANG Yu  WANG Liang-Fen  et al
Abstract:Objective To investigate the effect of ligustilide (LIG) on low potassium-induced apoptosis in primary cultured cerebellar granule neurons (CGN). Methods Apoptosis was induced by low potassium in cultured neonatal rat CGN in vitro. The CGN was divided into control/model/CGP54626+LIG and LIG group. The neuronal viability of each group was measured by MTT assay. The protein expression levels of the key insulin-like growth factor 1 (IGF)-1 signaling effectors,including the phosphorylated IGF-1 receptor (IGF-1R), Akt, ERK1/2, CREB and activated caspase 3 were examined by Western blot analysis. Results LIG ranging from 2.5 to 20 μmol/L could protect against low potassium-induced apoptosis of CGN in a concentration-dependent manner. 20 μmol/L LIG significantly induced upregulation of the phosphorylated levels of IGF-1, Akt, ERK1/2 and CREB, and downregulation of cleaved-caspase 3 expression, which could be blocked by a selective gamma-aminobutyric acid B (GABA B) receptor antagonist CGP54626. Conclusion LIG concentration-dependently protects against low potassium-induced apoptosis in CGN at least partly through GABA B receptor activation and its downstream IGF-1 signaling pathway.
Keywords:Ligustilide GABAB receptor IGF-1 signaling pathway Cerebellar granule neurons
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