银杏内酯诱导原代培养神经元低氧诱导因子1α的表达及与ERK通路的关系  

EXPRESSION OF HIF-1α INDUCED BY GINKGOLIDES IN PRIMARY CULTURED CORTICAL NENRONS AND THE RELATIONSHIP WITH ERK SIGNAL PATHWAY

作　　者：顾建兰[1] 季秋虹[2] 吴小梅[3] 金淑仪[3] 朱俐[3] 

机构地区：[1]南通大学医学院生物化学与分子生物学教研室,江苏南通226001 [2]南通大学附属医院神经内科,江苏南通226001 [3]航海医学研究所,江苏南通226001

出　　处：《中国应用生理学杂志》2007年第4期430-433,共4页Chinese Journal of Applied Physiology

基　　金：江苏省高校自然科学研究计划(04KJB310113);江苏省科技厅青年科学基金资助项目(BJ2000023)

摘　　要：目的:研究银杏内酯(Gin)对氯化钴(CoCl2)诱导的化学性缺氧原代培养神经元低氧诱导因子-α(HIF-1α)表达的影响及其与细胞外信号调节激酶(ERK)信号通路之间的关系。方法:以CoCl2(125μmol/L)诱导的原代培养胚胎小鼠大脑皮层神经元为缺氧模型,观察Gin(终浓度37.5mg/L)对神经细胞形态和活力的影响,Western blot HIF-1α和磷酸化ERK(p-ERK)的表达。运用ERK特异性抑制剂PD98059观察HIF-1α表达与ERK通路之间的关系。结果:Gin能明显提高CoCl2处理的神经细胞的活力。在正常培养的皮层神经元中HIF-1α和p-ERK的表达水平较低,CoCl2处理4h后表达水平明显上调;Gin预处理24h其表达强度进一步提高。PD98059能部分抑制CoCl2诱导的HIF-1α的表达,显著抑制p-ERK的表达;预加Gin能完全阻止该抑制作用。结论:Gin对CoCl2诱导的化学性缺氧损伤神经元有保护作用,该作用与HIF-1α表达上调、ERK通路的激活有关。To study the effects of ginkgolides（Gin） on the expression of hypoxia-inducible factor-1α（ HIF-1α） in primary cultured cortical neurons treated with CoCl2 and the relationship with ERK signal pathway. Methods： We observed the effects of Gin（37.5 mg/ L） on morphology and viability on primary cultured cortical neurons with treatment of COCl2 （ 125μmol/L）. The expression of HIF- 1α and p-ERK of neurons induced by CoCl2 pretreated with Gin were assessed by Western-blot. We analyzed the relationship between HIF-1α expression activated by Gin and ERK signal pathway with treatment of PD98059（ 100 μmol/L）, a selective inhibitor of ERK. Results： It was shown that Gin had protective effects on CoCl2 damaged neurons by raising the neuronal viability. Some basic expression of HIF-1α and p-ERK were observed in normal cultured cortical neurons. The expression of HIF-1α and p-ERK increased strikingly when treated with CoCl2 for 4 h. The levels of HIF-1α and p-ERK increased even more in the neurons pretreated with Gin for 24 h before CoCl2. The levels of HIF-1α and p-ERK were notably inhibited with pretreatment of PD98059, while Gin could prevent this inhibition.Conclusion： Gin has protective effects on neurons damaged by CoCl2 which might be related to the increase of the level of HIF-1α and the activation of ERK signal pathway.

关 键 词：银杏内酯 低氧诱导因子1Α 原代培养神经元 磷酸化细胞外信号调节激酶 

分 类 号：Q421[生物学—神经生物学]