核受体相关转录因子1(Nurr1)对大鼠脑缺血再灌注损伤的神经保护作用及机制  

Protective effect of nuclear receptor related 1(Nurr1)on nerves in rats with cerebral occlusion/reperfusion injury and its mechanism

作　　者：胡镝 谢雪梅 张徽 HU Di;XIE Xuemei;ZHANG Hui(Department of Pathology,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学基础医学院病理学教研室,重庆400016

出　　处：《细胞与分子免疫学杂志》2022年第3期231-236,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81771261)。

摘　　要：目的探讨核受体相关转录因子1(Nurr1)对大鼠脑缺血再灌注损伤的神经保护作用及机制。方法采用大脑中动脉闭塞线栓法建立SD大鼠大脑中动脉缺血再灌注损伤模型(MCAO/R),分为对照组、模型组、阴性病毒组和Nurr1过表达组。过表达Nurr1后,采用Longa改良神经功能评分法进行大鼠神经功能缺损评分,2,3,5氯化三苯基四氮唑(TTC)染色法检测脑梗死体积,免疫荧光组织化学染色检测微管相关蛋白2(MAP2)表达确定神经细胞损伤情况,相关试剂盒检测超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,Western blot法检测大鼠脑组织皮质层组织肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、B细胞淋巴瘤因子2(Bcl2)、Bcl2相关凋亡调节子X(BAX)的蛋白表达。结果与对照组相比,模型组中大鼠神经功能评分、脑梗死面积、MDA含量、TNF-α、IL-1β和BAX蛋白表达明显增加;MAP2阳性神经细胞数量、SOD活性和Bcl2蛋白表达明显降低;与模型组相比,过表达Nurr1后,神经功能评分、大鼠脑梗死面积、MDA含量、TNF-α、IL-1β和BAX蛋白表达则明显降低;MAP2阳性神经细胞数量、SOD活性和Bcl2蛋白表达明显增高。结论Nurr1可能通过抗氧化、抑制炎症反应,阻断线粒体凋亡信号通路介导的细胞凋亡,从而改善大鼠神经功能缺损,减轻脑缺血再灌注神经元损伤。Objective To investigate the protective effect of nuclear receptor related 1(Nurr1) on nerves in rats with cerebral occlusion/reperfusion injury and its mechanism. Methods Healthy male SD rats were chosen to construct the middle cerebral artery occlusion/reperfusion(MCAO/R) model. All rats were randomly divided into control group, model group, negative virus group, and Nurr1 over-expression group. Longa’s modified neurological severity score, Triphenyl tetrazolium chloride(TTC) staining, and immunofluorescence histochemical staining were applied respectively to detect the neurological injury, infarct volume, and density of microtubule associated protein-2(MAP2) positive nerve cells in rats after MCAO/R. Related kits were used to detect the activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA). The protein levels of Nurr1, tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), B cell lymphoma 2(Bcl2), and Bcl2-assaciated X protein(BAX) were detected by Western blot. Results Nurr1 over-expression improved the neurological outcome with lower modified neurological severity scores by decreasing infarct volume, content of MDA, and expressions of inflammatory mediators including TNF-α, IL-1β, and pro-apoptosis related protein BAX. Nurr1 over-expression significantly increased the density of MAP2 positive nerve cells, activity of SOD, and the expression of anti-apoptosis related protein Bcl2. Conclusion Nurr1 may alleviate the cerebral ischemic damage by resisting oxidation, reducing inflammation, and inhibiting mitochondrial apoptotic signaling pathway-mediated cell apoptosis.

关 键 词：脑缺血再灌注损伤 核受体相关转录因子1(Nurr1) 炎症反应 细胞凋亡 抗氧化 

分 类 号：R743.31[医药卫生—神经病学与精神病学] R364.5[医药卫生—临床医学]