FTY720通过激活CaMKK/Akt通路减轻全脑缺血再灌注损伤  

FTY720 reduced cerebral ischemic-reperfusion injury through CaMKK/Akt pathway activation

作　　者：许静[1] 刘志安[2] 高殿帅[2] 

机构地区：[1]徐州医学院机能学实验中心,江苏徐州221004 [2]徐州医学院解剖学教研室,江苏徐州221004

出　　处：《中风与神经疾病杂志》2012年第12期1070-1072,共3页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(No.81171141);江苏省高校自然科学基金(No.10KJB310016)

摘　　要：目的采用大鼠全脑缺血再灌注(I/R)模型,观察1-磷酸鞘氨醇(S1P)受体激动剂芬戈莫德(FTY720)对海马组织Ca2+/CaM依赖的蛋白激酶的激酶CaMKK表达水平和Akt磷酸化水平的影响以及对缺血再灌注后神经元的保护作用。方法制备全脑缺血大脑四动脉结扎模型,采用免疫印迹技术检测FTY720和CaMKK抑制剂STO-609对缺血后海马CA1区CaMKK表达、Akt磷酸化水平的影响,采用TUNEL检测FTY720和STO-609对缺血后海马神经元凋亡的影响。结果 FTY720降低缺血后海马CA1区神经元凋亡细胞数(P<0.05),而且在缺血复灌1d提高了CaMKK表达水平、Akt磷酸化水平(P<0.05),而STO-609可以降低其两者升高的水平(P<0.05)。结论 FTY720对缺血复灌后神经元有抗凋亡作用而且可能的分子机制是激活了CaMKK/Akt信号通路。Objective To observe the effect of sphingosine 1-phosphate receptor（S1P） agonists FTY720 on the level of calcium/calmodulin-dependent protein kinase kinase（CaMKK） expression,Akt phosphorylation and neuronal death in rats with cerebral isehemia-reperfusion（I/R）.Methods Transient cerebral ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats.FTY720 and CaMKK inhibitor STO-609 treatment on CaMKK expression and Akt phosphorylation in cytosol extracts of hippocampus CA1 region was observed by Western blotting,and effect on the neuronal apoptosis of CA1 neurons in rat hippocampus was detected using TUNEL assay.Results Pretreatment of FTY720 increased the number of the surviving CA1 pyramidal cells of hippocampus（P0.05）.Furthermore,FTY720 pretreatment enhanced CaMKK expression and Akt phosphorylation in I/R1d（P0.05）,which were reversed by STO-609.Conclusion FTY720 exerts the neuroprotective effect via activation of CaMKK/Akt pathway.

关 键 词：脑缺血 CaMKK FTY720 

分 类 号：R743.3[医药卫生—神经病学与精神病学]