PI3K/AKT信号途径在大鼠脑源性神经干细胞中的作用  

A Role for the Phosphatidylinositol 3-kinase(PI3K)/Akt Signaling Pathway in Rat Brain-derived Neural Stem Cells

作　　者：王爽[1] 谢鹏[1] 赵裕光[2] 贾延劼[1] 牟君[1] 王运良[1] 吕发金[3] 

机构地区：[1]重庆医科大学附属第一医院神经内科神经病学研究所,重庆400016 [2]重庆医科大学附属第一医院普外科,重庆400016 [3]重庆医科大学附属第一医院放射科,重庆400016

出　　处：《江西医学院学报》2005年第5期1-3,F0002,共4页Acta Academiae Medicinae Jiangxi

基　　金：国家自然科学基金资助项目(No.330370500);中国博士后科学基金资助项目(No.2003033363)

摘　　要：目的探讨磷脂酰肌醇-3激酶(phosphatidylinositol-3 kinase,PI3K)/AKT信号途径在体外培养神经干细胞存活、分化中的作用。方法分为对照组、PI3K特异性抑制剂LY294002组(LY294002浓度分别为2μmol/L,5μmol/L,10μmol/L);采用间接免疫荧光法检测Nestin、NF-200和GFAP的表达;TUNEL评价细胞凋亡率;Western Blot法检测磷酸化的AKT的表达。结果随着LY294002浓度增大,神经干细胞的形态变化逐渐明显,而且细胞凋亡率也逐渐增加。低浓度时(2μmol/L)神经干细胞凋亡率与对照组无显著性差异(P>0.05);高浓度时(5μmol/L、10μmol/L)神经干细胞凋亡率与对照组、低浓度组有极显著性差异(P<0.01)。Western Blot结果提示,随着LY294002浓度增大,磷酸化AKT的表达逐渐减弱。结论本研究提示神经干细胞存活依赖于PI3K/AKT途径的活化,其机制可能是PI3K/AKT活化后,抑制了细胞凋亡事件的发生,但PI3K/AKT途径可能在神经干细胞分化中的作用甚微。Objective Phosphatidylinositol 3-Kinase（PI3K）is a protein enzyme. We primarily discussed the function of PI3K/AKT signal pathway in proliferation and differentiation of neural stem cells（NSCs）. Methods In the base of cultured NSCs, we divided randomly into control groups and LY294002 groups （2μmol/L,5μmol/L,10μmol/L）. LY294002 is the distinctive inhibitor of PI3K. We detected the expression of Nestin, NF-200 and GFAP by indirect immunofluo- rescence. We estimated the ratio of cell apoptosis by TUNEL staining and detected the expression of phosphorylated AKT by Western blot. Results With the increase of LY294002 concentration, the morphology of NSCs have obvious effections in groups. The apoptosis ratio of NSCs was increased gradually. In lower concentration（2 μmol/L）, the apoptosis ratio of NSCs have no obvious effections compared to control group （P 〉 0. 05）;However in higher concentration （5 μmol/L, 10 μmol/L）, they have obvious effections compared to control group and lower concentration group（P〈0.01）. The results of Western blot indicated that the expression of phosphorylated AKT decreased when LY294002 increased. Conclusion The study indicated that the survival ofNSCs depended on the activation of PI3K/AKT pathway. But PI3K/AKT pathway may have little function in the diffe：rentiation of NSCs.

关 键 词：磷脂酰肌醇-3激酶(PI3K) AKT 神经干细胞 大鼠 动物 实验 

分 类 号：R-332[医药卫生]