锂剂通过阻遏STAT3激活而抑制星形胶质细胞分化的实验研究  

Suppression effect of lithium on astroglial differentiation through JAK/STAT3 dependent signal transduction pathway

作　　者：朱振中[1] 张长青[1] 金东旭[1] 历强[2] 贺西京[3] 

机构地区：[1]上海交通大学附属第六人民医院骨科,200233 [2]山东省青岛市立医院骨科 [3]西安交通大学医学院第二附属医院骨二科

出　　处：《中华神经外科杂志》2014年第4期414-418,共5页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金（81200944/H0910）;中国博士后基金（2012M520044）

摘　　要：目的探讨锂剂抑制神经干细胞向星形胶质细胞分化是否与胶质分化经典调控通路JAK／STAT3有关。方法采用Westernblot和免疫细胞化学法检测分化时STAT3通路激活标志性蛋白P—Tyr-705STAT3的表达及锂剂的作用；再用激动剂5-氨基咪唑-4甲酰胺核苷酸（AICAR）上调该通路活性，于不同时间点观察锂剂对其是否有拮抗作用。结果神经干细胞分化时，对照组磷酸化STAT3上升约17倍，3mmol／L锂剂组仅上升约4倍（P〈0．01）；AICAR可显著诱导磷酸化STAT3表达及GFAP表达（P〈0．05），但上述诱导作用可被锂剂所阻断。结论锂剂影响神经干细胞向星形胶质细胞分化与其对JAK／STAT3通路活性抑制有关。Objective To investigate the effect of Lithium on astrogliogenesis by neural stem/ progenitor cells （NSCs） and its canonical regulating JAK/STAT3 singal transduetion pathway. Methods Under NSCs differentiating condition, we firstly detected the P -Tyr -705 STAT3 among total STAT3 expression to test the lithium effect on JAK/STAT3 activation, then we used AICAR, which was an specific STAT3 agonist, to up - regulate STAT3 activity. After validating the effect of AICAR on inducing STAT3 activation and astrogliogenesis, we tested whether Lithium could block the effect of AICAR by detecting P- Tyr- 705 STAT3 and GFAP expression. Results Lithium dramatically reduced the JAK/ STAT3 activation of differentiating NSCs, P - Tyr - 705 STAT3 expression increased by 17 folds （ P 〈 0.01 ）. Pre - treatment of 3 mmol/L Lithium abolished the induced JAK/STAT3 activation after 24h and GFAP expressing on 3 days （ P 〈 0. 05 ）, as detected by Western blotting and immunocytochemistry. Conclusions Lithium could suppress astroglial differentiation through JAK/STAT3 dependent signal transduetion pathway.

关 键 词：锂剂 星形胶质细胞 神经干细胞 STAT3转录因子 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]