细胞外信号调节激酶1/2在谷氨酸引起的星形胶质细胞炎症反应中的作用

Effect of extracellular signal-regulated kinase 1/2 in glutamate-induced inflammatory reaction of culture astroglia in vitro

目的观察谷氨酸诱导星形胶质细胞激活炎症细胞因子表达及细胞外信号调节激酶1/2(ERK1/2)的表达情况,探讨ERK1/2在星形胶质细胞激活炎症细胞因子中的作用。方法传代体外培养的大鼠星形胶质细胞,分别用终浓度为20μmol/L和50μmol/L的谷氨酸作用30 min。应用ERK上游激酶MEK特异性阻断剂PD98059(10μmol/L)阻断ERK信号转导通路,Western blot观察阻断前后星形胶质细胞磷酸化ERK1/2、白细胞介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)和环氧合酶-2(COX-2)蛋白表达水平的改变。结果谷氨酸使体外培养星形胶质细胞磷酸化ERK1/2蛋白表达明显增加,同时,使iNOS、COX-2I、L-1β表达明显增加;PD98059可完全阻断谷氨酸引起的ERK1/2表达增加,也可抑制谷氨酸引起的iNOS、COX-2、IL-1β蛋白表达增加。结论ERK1/2信号转导通路参与谷氨酸引起体外培养星形胶质细胞炎症反应的作用。

Objective It is to observe the expression of glutamate induce astroglia activated inflammatory and extracellular signal-regulated kinase 1/2 （ERK 1/2）, and explore the effect of extracellular signal-regulated kinasel/2 in astroglia activated inflammatory. Methods The passage astroglia of rats cultured in vitro was treated by glutamate for 30 minutes with the density of 20 μmol/L and 50 μmol/L. The signal transduction pathway of MEK was inhibited by upstream kinase of ERK PD98059. The expressions changes of extracellular regulated protein kinases1/2 （ERK1/2）, interleukin- 1β （IL- 1β）,inducible nitric oxide synthase （iNOS） and cycoxygenase 2 （COX - 2） were observed before and after inhibited. Results Glutamate could increase the level of P - ERK 1/2 obviously in astroglia cultured in vitro, and also increase the level of iNos, COX - 2, IL- 1β obviously. PD98059 could completely inhibit the increase of ERK 1/2 induced by glutamate, and also inhibit the increase of iNos, COX- 2, IL- 1β induced by glutamate. Conclusion ERK 1/2 signal transduction pathway is involved in glutamate induce astroglia activated inflammatory reaction.