p38 MAPK反义寡聚脱氧核苷酸阻断肢体缺血预处理诱导的脑缺血耐受  

P38 MAPK antisense oligodeoxynucleotide inhibited the brain ischemic tolerance induced by limb ischemic preconditioning

作　　者：孙晓彩[1] 李文斌[1] 李清君[1] 张敏[1] 羡晓辉[1] 李淑琴[1] 齐杰[1] 刘会茹[2] 

机构地区：[1]河北医科大学病理生理学研究室,石家庄050017 [2]河北科技师范学院,秦皇岛066004

出　　处：《中国应用生理学杂志》2010年第2期129-132,共4页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金(30770738);教育部博士点基金(20050089001);河北省自然科学基金(C200500720;C2008001042);河北省科技厅(072761901);河北省卫生厅(20090313);河北医科大学科研骨干人才培育计划资助项目

摘　　要：目的:观察p38MAPK反义寡聚脱氧核苷酸(As-ODN)对肢体缺血预处理(LIP)诱导的脑缺血耐受的影响。方法:48只永久凝闭双侧椎动脉的Wistar大鼠分为8组(n=6):sham组、LIP组、脑缺血损伤组、LIP+脑缺血损伤组、双蒸水+LIP+脑缺血损伤组、p38MAPKAs-ODN组和p38MAPKAs-ODN+LIP+脑缺血损伤组,p38MAPKAs-ODN的剂量又分为5nmol/5μl和10nmol/5μl。所有动物均在sham手术后或末次全脑缺血/再灌注后7天断头取脑,硫堇染色观察海马CA1区锥体神经元迟发性死亡情况。结果:sham组和LIP组均未见延迟性神经元死亡(DND)。与sham、LIP组相比,脑缺血损伤组出现了明显的DND,表现为组织学分级(HG)升高和锥体神经元密度(ND)下降(P<0.05)。LIP可显著抑制脑缺血损伤引起的DND。与LIP+脑缺血损伤组相比,p38MAPKAs-ODN+LIP+脑缺血损伤组出现了显著的DND,表现为HG升高、ND降低(P<0.05),且此种变化与p38MAPKAs-ODN的注射剂量呈明显正相关。结论:p38MAPKAs-ODN可阻断LIP诱导的脑缺血耐受,进一步证实了p38MAPK表达上调参与了LIP诱导的脑缺血耐受。Objective：To better assess the role of p38 MAPK,this project was designed to investigate whether intraventricular injection of antisense oligodeoxynucleotide （As-ODN） directed against the p38 MAPK of pyramidal neurons in hippocampus could affect the brain ischemic tolerance induced by limb ischemic preconditioning （LIP）.Methods：The rat 4-vessel occlusion global cerebral ischemic model was used.Forty-eight male Wistar rats with permanently occlusion of the bilateral vertebral arteries were divided into 8 groups （n=6）：sham,LIP,brain ischemic insult,LIP ＋ brain ischemic insult,distilled water ＋ LIP ＋ brain ischemic insult,p38 MAPK As-ODN and p38 MAPK As-ODN ＋ LIP ＋ brain ischemic insult （two doses of 5 nmol/5 μl and 10 nmol/5 μl were used） groups.Thionin staining was used for observing histological changes of the hippocampus.Results：No significant delayed neuronal death （DND） was detected in the CA1 hippocampus of the rats that underwent sham and LIP operation.Brain ischemic insult for 8 min induced obvious DND as represented with the increase in histological grade （HG） and decrease in neuronal density （ND） significantly compared with sham and LIP groups.LIP protected the CA1 hippocampal pyramidal neurons against DND induced by global brain ischemic insult,suggesting the occurrence of brain ischemic tolerance.However,pretreatment with p38 MAPK As-ODN effectively blocked the ischemic tolerance induced by LIP in a dose dependent manner.Conclusion：It could be concluded that p38 MAPK plays an important role in the brain ischemic tolerance induced by LIP.

关 键 词：P38MAPK p38MAPKAs-ODN 肢体缺血预处理 脑缺血耐受 海马 

分 类 号：R363[医药卫生—病理学]