基于Nrf-2/ARE通路探讨鸢尾素对缺血缺氧小鼠脑组织的保护作用  

Protection effect of irisin on brain tissue of ischaemic hypoxia mice

作　　者：杨斯宇 方璐[1] YANG Si-yu;FANG Lu(Department of Sensile Disease,Qun Li Hospital,The First Affiliated Hospital of Harbin Medical University,Harbin 150010,China)

机构地区：[1]哈尔滨医科大学附属第一医院群力院区老年病科,黑龙江哈尔滨150010

出　　处：《哈尔滨医科大学学报》2024年第4期350-354,共5页Journal of Harbin Medical University

摘　　要：目的研究鸢尾素激活核因子E-2-相关因子-2(nuclearfactor erythroid-2-related factor-2,Nrf-2)/抗氧化反应元件(anti-oxidant response element,ARE)信号通路对缺血缺氧小鼠脑损伤的保护作用。方法将32只7周龄雄性C57BL/6N清洁级小鼠分为假手术组、模型组、鸢尾素低剂量组及鸢尾素高剂量组(每组8只),采用结扎颈总动脉结合缺氧法构建鼠缺血缺氧动物模型,对照组不接受结扎及缺氧处理。水迷宫实验检测小鼠的认知功能;HE染色观察脑组织病理改变;透射电子显微镜观察神经元结构改变;商业试剂盒测定脑组织中过氧化氢酶(catalase,CAT)、超氧化物歧化酶(super oxide dimutese,SOD)和丙二醛(malondialdehyde,MDA);Western blot法检测Nrf-2、血红素氧合酶1(heme oxygenase-1,HO-1)的蛋白表达。结果与模型组比较,鸢尾素组小鼠在水迷宫试验中平均逃避潜伏期明显缩短,平均跨越平台次数明显增加(P<0.05);组织切片染色显示模型组小鼠大脑皮层区可见大量神经元细胞胞质空泡化,神经元成网状排列,出现广泛的神经元损伤,鸢尾素低、高剂量组神经元水肿及变性程度逐渐改善;透射电子显微镜结果显示,鸢尾素能够改善神经元结构异常;与假手术组小鼠比较,模型组小鼠脑组织中CAT活性及SOD活性明显降低,MDA含量显著升高,鸢尾素了增加小鼠脑组织中CAT活性及SOD活性并降低MDA含量(P<0.05);Western blot结果显示,与假手术组小鼠比较,模型组小鼠Nrf-2、HO-1水平显著降低,鸢尾素增加了小鼠脑组织中Nrf-2和HO-1的水平(P<0.05)。结论鸢尾素可能通过调节大脑氧化应激改善缺血缺氧小鼠认知障碍。Objective To study the protection effect of irisin activating the nuclearfactor erythroid-2-related factor-2(Nrf-2)/anti-oxidant response element(ARE)signaling pathway on brain injury in mice with ischaemic hypoxia.Methods Thirty-two 7-week-old male C57BL/6N clean grade mice were divided into sham surgery group,model group,low-dose irisin group,and high-dose irisin group(n=8).Rat model of ischaemic hypoxia was constructed using ligation of the common carotid artery combined with hypoxia,while the control group did not receive ligation or hypoxia treatment.The water maze experiment was used to detect the cognitive function of mice;HE staining was used to observe pathological changes in brain tissue;Transmission electron microscopy was used to observe neuronal structural changes;Com-mercial kits were used to measure catalase(CAT),super oxide dimutese(SOD)and malondialdehyde(MDA)levels in brain tissues;Western blot method was used to detect the protein expression of Nrf-2 and heme oxygenase-1(HO-1).Results Compared with the model group,mice in irisin group had a significantly shorter average escape latency and an increased average number of crossing platforms in the water maze test(P<0.05);Tissue section staining showed that a large number of neuronal cell cytoplasmic vacuolization was found in the cerebral cortex area of the model group mice,with neurons arranged in a network,resulting in extensive neuronal damage,the degree of neuronal edema and degeneration gradually improved in the low and high dose groups of irisin;The results of transmission electron microscopy showed that irisin improved neuronal structural abnormalities;Compared mice in the sham operated group,the CAT and SOD activities in the brain tissue of the model group mice were significantly reduced,and the MDA content was significantly increased,irisin increased the CAT and SOD activities in the mouse brain tissue and decreased the MDA content(P<0.05);Western blot results showed that compared with the sham operated group mice,the model group mice had

关 键 词：鸢尾素 缺血缺氧 小鼠 Nrf-2/ARE信号通路 

分 类 号：R743.33[医药卫生—神经病学与精神病学]