自由基在肢体缺血预处理诱导的大鼠脑缺血耐受中的作用  

Role of free radicals in cerebral ischemic tolerance of rats induced by limb ischemic preconditioning

作　　者：冯荣芳[2] 袁强[1] 张晓[1] 李淑琴[1] 孙晓彩[1] FENG Rongfang;YUAN Qiang;ZHANG Xiao;LI Shuqin;SUN Xiaocai(Department of Pathophysiology,Hebei Medical University,Shijiazhuang 050017,China;Department of Neurology,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北医科大学病理生理学研究室,河北石家庄050017 [2]河北省人民医院神经内科,河北石家庄050051

出　　处：《中国病理生理杂志》2023年第4期599-607,共9页Chinese Journal of Pathophysiology

基　　金：Supported by grants from National Natural Science Foundation of China(No.31100781);Natural Science Foundation of Hebei Province,China(No.C2011206040).

摘　　要：目的:我们前期的研究证实,肢体缺血预处理(limb ischemic preconditioning,LIP)能够诱导大鼠的脑缺血耐受,并且p38 MAPK和ERK在其中发挥了重要的神经保护作用。本研究旨在探讨自由基是否参与LIP诱导的大鼠脑缺血耐受和p38 MAPK和ERK表达的上调。方法:128只永久凝闭双侧椎动脉的Wistar大鼠,随机分为假手术(sham)组(n=16)、全脑缺血(cerebral ischemia,CI)组(n=16)、LIP+CI组(n=16)、DMTU(自由基清除剂)+LIP+CI组(n=64)和DMTU+sham组(n=16)。各组6只大鼠于末次手术后7 d取材,硫堇染色观察海马CA1区锥体神经元迟发性死亡(delayed neuronal death,DND)情况;另外10只大鼠应用免疫组织化学和Western blot观察海马CA1区p38 MAPK和ERK的表达。结果:致死性全脑缺血引起大鼠海马CA1区出现明显的DND。然而,LIP明显逆转了上述损伤性变化:与CI组比较,CA1区组织学分级降低、神经元密度增加(P<0.01);此外,与CI组比较,海马CA1区p38 MAPK和ERK的表达明显上调(P<0.01)。与LIP+CI组相比,LIP前经股静脉给予自由基清除剂DMTU,可部分逆转LIP的脑保护作用,也可部分阻断LIP对脑缺血大鼠海马CA1区p38 MAPK和ERK表达的上调作用(P<0.01)。结论:自由基参与了LIP诱导的大鼠脑保护作用和p38 MAPK和ERK表达的上调。AIM:To explore whether free radicals participate in cerebral ischemic tolerance and the up-regulation of p38 MAPK and ERK signaling pathways in rats induced by limb ischemic preconditioning(LIP).METHODS:A total of 128 Wistar rats with permanent occlusion of bilateral vertebral arteries were randomly divided into sham group(n=16),cerebral ischemia(CI)group(n=16),LIP+CI group(n=16),DMTU(a free radical scavenger)+LIP+CI group(n=64)and DMTU+sham group(n=16).Six rats in each group were used to observe the delayed neuronal death(DND)in hippocampal CA1 region by thionin staining at 7 d after the end of operation.Other 10 rats in each group were used to detect the expression of p38 MAPK and ERK in hippocampal CA1 region by immunohistochemistry and Western blot.RE⁃SULTS:Lethal CI resulted in obvious DND in hippocampal CA1 region.However,LIP reversed the above injurious changes,represented by the decrease in histological grade and the increase in neuronal density compared with CI group(P<0.01).Moreover,LIP significantly up-regulated the expression of p38 MAPK and ERK in hippocampal CA1 region compared with CI group(P<0.01).Administration of free radical scavenger DMTU via femoral vein before LIP partially reversed the neuroprotective effect of LIP,and blocked the up-regulation of p38 MAPK and ERK expression in hippocampal CA1 region in rats compared with LIP+CI group(P<0.01).CONCLUSION:Free radicals are involved in the neuroprotection and up-regulation of p38 MAPK and ERK expression induced by LIP in rats.

关 键 词：自由基 肢体缺血预处理 脑缺血耐受 p38 MAPK信号通路 ERK信号通路 

分 类 号：R743[医药卫生—神经病学与精神病学] R363[医药卫生—临床医学]