MAPKs阻断剂U0126对体外培养神经细胞缺氧损伤后细胞损伤和水通道蛋白4表达影响的研究  

Effect of MAPKs Signal Transduction Pathway Inhibitor U0126 on Cellular Injury and AQP4 Expression in Cultured Neurons with Hypoxic Injury

作　　者：呙登俊[1] 赵永波[1] 陈英辉[1] 王乃东[1] 刘文文[1] 

机构地区：[1]上海第一人民医院神经科上海交通大学附属第一人民医院神经科,200080

出　　处：《中国临床神经科学》2006年第3期234-237,共4页Chinese Journal of Clinical Neurosciences

基　　金：上海市重点基金项目(024119037);上海市引进海外高层次留学人员专项基金资助项目(20040105)

摘　　要：目的:研究丝裂原活化蛋白激酶信号通路抑制剂U0126对体外神经细胞缺氧损伤后细胞生长状态及水通道蛋白4(AQP4)表达的影响。方法:取出生1d的SD大鼠皮质神经细胞进行缺氧培养致细胞损伤,分为处理组和缺氧组,前者给予U0126,后者给予二甲基亚砜作为对照,检测AQP4的表达情况及细胞外信号调节蛋白激酶(ERK1/2)和Ets样因子(ELK1)蛋白磷酸化水平的变化。结果:缺氧损伤后细胞状态不佳,AQP4表达升高。给予U0126后ERK1/2和ELK1磷酸化水平降低,细胞状态有所改善,同时AQP4的表达降低。结论:缺氧损伤后细胞肿胀与AQP4的表达增高有关,U0126可抑制AQP4的表达,减轻细胞损伤。Aim： To study the effect of U0126 on cellular injury and the expression of AQP4 in cultured neurons after hypoxic injury. Methods： Brains from 1 day postnatal SD rats were taken for in vitro neuron culture. 3 days later, neurons were treated with hypoxia and then divided into treatment group and hypoxia group randomly, the former accepted 10μmol· L^-1 U0126, while the later accepted dimethyl sulfoxide （DMSO） of the same volume. 2 days later, techniques such as immunocytochemistry, Western blot and RT-PCR were used to detect the expression level of aquaporin4 （AQP4） in neurons during acute cellular edema stage, as well as the phosphorylation level of signal-regulated kinase 1 and 2 （ERK1/2） and Ets-like factors 1 （ ELK1 ）, both of which are key proteins of MAPKs signal transduction pathway. Results： Compared with that of normal group, AQP4 expression in hypoxia and treatment group showed obviously statistical increase （P 〈 0.01）, as well as evident cellular swelling. And the level of AQP 4 expression in treatment group was lower than that of hypoxia group. Conclusions： There is a relationship between cellular edema and the overexpression of AQP 4. U0126 can inhibit the overexpression of AQP 4 and then reduce cellular edema.

关 键 词：缺氧 水通道蛋白4 丝裂原活化蛋白激酶 

分 类 号：Q189[生物学—神经生物学]