U0126对缺血性脑损伤大鼠脑内水通道蛋白-4表达的影响  

Effects of U0126 on brain edema and aquaporin 4 expression in rat brains after cerebral ischemic injury

作　　者：呙登俊[1] 陈英辉[1] 赵永波[1] 王乃东[1] 

机构地区：[1]上海第一人民医院神经科,200080

出　　处：《中华神经科杂志》2006年第3期172-175,共4页Chinese Journal of Neurology

基　　金：上海市重点基金资助项目(024119037);上海市引进海外高层次留学人员专项基金资助项目(20040105);上海市卫生局基金资助项目(034034)

摘　　要：目的研究水通道蛋白-4(aquaporin4,AQP4)在缺血性脑损伤大鼠脑内的表达,及丝裂原活化蛋白激酶(MAPKs)信号转导通路抑制剂U0126对其表达的影响。方法用线栓法建立缺血性脑损伤大鼠模型,测定脑组织含水量及伊文斯蓝含量,并采用免疫组织化学、Westernblot和逆转录-聚合酶链反应技术,检测AQP4的表达。测定预先经侧脑室给予U0126后MAPKs信号通路关键蛋白ERK1/2和ELK1磷酸化水平,同时观察U0126对脑水肿和AQP4表达的影响。结果正常组AQP4表达较低[蛋白(吸光度值,下同):123·1±1·0,mRNA(吸光度比值,下同):0·173±0·017],在缺血损伤后表达升高(蛋白:153·6±0·8,mRNA:0·400±0·015),脑组织含水量及伊文斯蓝含量增加,给予U0126后AQP4的表达和脑组织含水量降低(蛋白:149·0±1·1,mRNA:0·328±0·010,P<0·01),同时ERK1/2和ELK1磷酸化水平降低。结论缺血性损伤后AQP4表达上升,脑水肿明显,预先给予U0126可抑制AQP4的表达,减轻脑水肿。Objective To investigate the effect of U0126 on brain edema and the expression of aquaporin 4 （AQP4） in rat brains after cerebral ischemic injury. Methods Totally 48 healthy male SD rats were divided randomly into ischemia group, treatment group and normal group. Rats in ischemia group and treatment group underwent middle cerebral artery occlusion by using an intraluminal thread method. Thirty minutes before operation, the rats in treatment group were injected into lateral cerebral ventricle with U0126, while rats in ischemia group accepted normal saline. 24 hours after operation, the water content and Evans Blue in rat brains were determined as to exploring the degree of brain edema. Immunohistochemistry, Western blot and RT-PCR technique were applied to detect AQP4, p-ERK1/2 and p-ELK1. Results Compared with normal group, the water content and AQP4 expression in ischemia group were increased obviously. The water content and AQP4 expression in treatment group （protein ： 149.0 ± 1.1, mRNA ：0. 328 ± 0. 010） were lower than those in ischemia group （ protein： 153. 6 ± 0. 8, mRNA： 0. 400 ± 0. 015, P 〈 0. 01 ）. Meanwhile, pERK1/2 and p-ELK1 in treatment group were lower than those in ischemia group. Conclusion There should be evident brain edema after cerebral ischemic injury, accompanied by the overexpression of AQP4. U0126 pretreatment should be able to inhibit the overexpression of AQP4 and reduce the brain edema.

关 键 词：脑缺血 脑水肿 水孔蛋白类 丁二烯类 腈类 大鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]