藁本内酯对低钾大鼠小脑颗粒神经元凋亡的保护作用  

Protective Effect of Ligustilide Against Low Potassium Induced Apoptosis in Cultured Rat Cerebellar Granule Neurons

作　　者：李玲姣[1] 王宇[1] 王良芬[1] 杜俊蓉[1] 

机构地区：[1]四川大学华西药学院药理学系,成都610041

出　　处：《四川大学学报（医学版）》2015年第1期42-46,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81072636)资助

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（2.5~20μmol/L）可浓度依赖性抑制大鼠CGN的低钾性凋亡、提高其存活率;20μmol/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。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, ERK 1/2, 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 （GABAB） receptor antagonist CGP54626. Conclusion LIG concentration-dependently protects against low potassium-induced apoptosis in CGN at least partly through GABAB receptor activation and its downstream IGF-1 signaling pathway.

关 键 词：藁本内酯 GABAB受体 IGF-1信号通路 小脑颗粒神经元 

分 类 号：R285.5[医药卫生—中药学]