肢体缺血后处理通过Nrf2/ARE通路对大鼠脑缺血再灌注损伤的影响

目的 探讨肢体缺血后处理通过核转录因子红细胞系相关因子-2(Nrf2)/抗氧化反应元件(ARE)通路对大鼠脑缺血再灌注损伤(CIRI)的影响.方法 45只大鼠随机分为假手术组(S组)、缺血再灌注组(I/R组)、肢体缺血后处理组(LpostC组)3组,每组15只.分别建立I/R组、LpostC组的脑缺血再灌注模型,在该基础上建立LpostC组的肢体缺血后处理模型.于造模后24 h分别比较三组的神经功能缺损评分、脑梗死体积、脑组织病理形态学、Nrf2和超氧化物歧化酶(SOD)1蛋白表达.结果 S组大鼠无神经功能缺损、脑梗死,LpostC组神经功能缺损评分和脑梗死体积低于I/R组(均P<0.05);S组脑组织无病理学改变,I/R组呈急性缺血性改变,LpostC组病理学改变轻于I/R组;I/R组、LpostC组的Nrf2和SOD1蛋白表达均高于S组,且LpostC组高于I/R组(均P<0.05).结论 肢体缺血后处理上调大鼠Nrf2和SOD1蛋白表达,通过激活Nrf2/ARE信号通路减轻CIRI.

Effect of limb ischemic post-conditioning on rats with cerebral ischemia-reperfusion injury through Nrf2/ARE pathway

Objective To investigate the effect of limb ischemic post-conditioning on rats with cerebral ischemia-reperfusion injury(CIRI) through nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE) pathway.Methods A total of 45 rats were randomly divided into sham-operation group(Group S),ischemia-reperfusion group(Group I/R) and limb ischemic post-conditioning group(LpostC group),with 15 cases in each group.The limb ischemic post-conditioning models were established in LpostC group on the basis of the cerebral ischemia-reperfusion models established in Group I/R and LpostC group respectively.After 24 hours of modeling,the neurological function defect score,cerebral infarction volume,pathomorphological changes in brain tissues,protein expressions of Nrf2 and superoxide dismutase(SOD)1 were compared among the three groups respectively.Results There were no neurological function defect or cerebral infarction in Group S,the neurological function defect score and cerebral infarct volume of the LpostC group were less than those of Group I/R(all P<0.05).There were no pathological changes in brain tissues in Group S,acute ischemic changes were found in Group I/R,and the pathological changes in LpostC group were milder than those in Group I/R;the protein expressions of Nrf2 and SOD1 in Group I/R and LpostC group were higher than those in Group S,and the expressions in LpostC group were higher than those in Group I/R(all P<0.05).Conclusion Limb ischemia post-conditioning can up-regulate the protein expressions of Nrf2 and SOD1 in rats and relieve CIRI through activating the Nrf2/ARE signaling pathway.