p38 MAPK反义寡聚脱氧核苷酸抑制脑缺血预处理诱导脑缺血耐受过程中GLT-1表达上调  

p38 MAPK antisense oligodeoxynucleotide inhibited up-regulation of GLT-1 during induction of brain ischemic tolerance induced by cerebral ischemic preconditioning

作　　者：王佳磊[1] 蒋孟洋[1] 张孟岳 王文帅[3] 李力[4] 张玲燕[1] 李文斌[1,5] 张敏[1,5] 

机构地区：[1]河北医科大学病理生理学教研室,河北石家庄050017 [2]河北医科大学临床医学“5+3”一体化2015级,河北石家庄050017 [3]河北省胸科医院胸外科,河北石家庄050041 [4]河北医科大学第二临床医学院科技处,河北石家庄050000 [5]河北省脑老化与认知神经重点实验室,河北石家庄050031

出　　处：《中国药理学通报》2017年第9期1253-1259,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31271149,81271454);河北省自然科学基金资助项目(No H2015206492);河北省人才培养工程资助项目(No A201400544)

摘　　要：目的观察p38 MAPK反义寡聚脱氧核苷酸(ASODNs)是否影响大鼠脑缺血预处理(CIP)诱导脑缺血耐受过程中GLT-1蛋白的表达。方法 80只健康Wistar大鼠,♂,永久凝闭椎动脉,随机分为6组:(1)假手术(sham)组(n=10);(2)CIP组(n=10);(3)脑缺血损伤(Ⅱ)组(n=10);(4)CIP+Ⅱ组(n=10);(5)p38 MAPK AS-ODNs+CIP+Ⅱ组(n=30);(6)p38 MAPK S-ODNs+CIP+Ⅱ组(n=10)。(5)组中根据p38 MAPK AS-ODNs所用剂量不同分为5 nmol、10 nmol及15 nmol亚组(n=10);p38 MAPK S-ODNs的剂量为15nmol。所有动物均在sham手术或末次脑缺血/再灌注后6 h和2 d取材,Western blot和(或)免疫组织化学法检测p-p38MAPK及GLT-1蛋白的表达。结果 CIP引起p-p38 MAPK适度升高和GLT-1明显升高,并抑制Ⅱ引起的p-p38 MAPK过度升高及GLT-1表达下调;注射p38 MAPK AS-ODNs抑制CIP诱导脑缺血耐受过程中p-p38 MAPK和GLT-1的表达上调,呈剂量依赖性。结论 p38 MAPK AS-ODNs阻断CIP诱导脑缺血耐受过程中GLT-1表达上调。Aim To investigate the effect of p38 MAPK AS-ODNs on the expression of GLT-1 during the induction of brain ischemic tolerance induced by cerebral ischemic preconditioning（ CIP）. Methods Eighty healthy male Wistar rats with permanent occlusion of the bilateral vertebral arteries were randomly divided into 6 groups：（1）Sham group（ n = 10）;（2）CIP group（ n = 10）;（3）ischemic insult（ Ⅱ） group（ n = 10）;（4）CIP ＋ Ⅱ group（ n = 10）;（5）p38 MAPK AS-ODNs＋ CIP ＋ Ⅱ group（ n = 30）;（6）p38 MAPK S-ODNs ＋CIP ＋ Ⅱ group（ n = 10）. Group（5） was divided into 5nmol,10 nmol and 15 nmol subgroups according to the dose of p38 MAPK AS-ODNs（ n = 10）. The dose of p38 MAPK S-ODNs was 15 nmol. All the rats were sacrificed 6 h and 2 d after the sham operation or the last time of global brain ischemia reperfusion. Western blot and immunohistochemistry analysis were used for detecting the expression of p-p38 MAPK and GLT-1protein. Results CIP moderately up-regulated the expression of p-p38 MAPK and significantly up-regulated the expression of GLT-1 protein,inhibited the excessively up-regulation of p-p38 MAPK and the down-regulation of GLT-1 induced by ischemic insult. p38 MAPK AS-ODNs significantly inhibited the up-regulation of p-p38 MAPK and GLT-1 protein in a dose-dependent manner during the induction of brain ischemic tolerance by CIP. Conclusion p38 MAPK AS-ODNs inhibit the up-regulation of GLT-1 during the induction of brain ischemic tolerance induced by CIP.

关 键 词：p38 MAPK GLT-1 AS-ODNs 脑缺血预处理 海马 大鼠 

分 类 号：R-332[医药卫生] R322.81