摘要
背景:实验证明,有氧运动能够改善脑损伤后大脑供血状态,在临床中配合有氧运动治疗阿尔茨海默症收效甚益,但对其机制的研究仍处于空白阶段。目的:基于AMPK/eNOS/NF-κB信号通路探讨有氧运动对β-淀粉样蛋白1-42致痴呆大鼠大脑的保护作用机制。方法:将80只SPF级SD雄性大鼠随机分为4组(n=20):假手术组、模型组、有氧运动组和抑制剂组,除假手术组外其余大鼠采用β-淀粉样蛋白1-42诱导构建阿尔茨海默病模型;假手术组切开硬脑膜后注射2μL生理盐水。造模结束后第3天,抑制剂组腹腔注射50 mg/L AMPK Compound C 2 mL;其余组注射等量生理盐水。注射后有氧运动组和抑制剂组进行12周有氧运动训练,假手术组和模型组不进行任何治疗。运动结束后,通过水迷宫实验和跳台实验检测各组大鼠的空间学习记忆能力的变化;依次采用激光散斑成像、苏木精-伊红染色、ELISA法和免疫荧光法检测各组大鼠大脑皮质血流变化、脑梗死体积、脑组织内神经元的损伤、脑组织中白细胞介素1β、白细胞介素6和肿瘤坏死因子α表达水平及核转录因子κB的核移位;Western blot检测p-AMPK、p-eNOS和核转录因子κB蛋白的表达水平。结果与结论:①与假手术组相比,模型组大鼠逃避潜伏期明显延长,经过原平台所在象限的次数明显更低,大鼠大脑皮质血流灌注量明显减少,脑组织内细胞凋亡率及白细胞介素1β、白细胞介素6和肿瘤坏死因子α表达水平升高,脑组织细胞内核转录因子κB核移位荧光强度明显增强,且脑组织中p-AMPK、p-eNOS明显降低,核转录因子κB蛋白表达明显升高(均P<0.05);与模型组相比,有氧运动组逃避潜伏期出现明显下降,经过原平台所在象限的次数明显增多,大鼠大脑皮质血流灌注量明显增加,脑组织内细胞凋亡率及白细胞介素1β、白细胞介素6和肿瘤坏死因子α表达水平降低,脑组织细胞内核转
BACKGROUND:Aerobic exercise has been experimentally proved to improve the blood supply of the brain after brain injury.In clinical practice,aerobic exercise is effective in treating Alzheimer’s disease,but the research on its mechanism is still at a blank stage.OBJECTIVE:To explore the mechanism by which aerobic exercise protects the brain of amyloidβ-protein(Aβ)1-42-induced dementia rats through the adenosine monophosphate activated protein kinase(AMPK)/endothelial nitric oxide synthase(eNOS)/nuclear factorκB(NF-κB)signaling pathway.METHODS:A total of 80 SPF Sprague-Dawley male rats were randomly divided into 4 groups(n=20 per group):sham operation group,model group,aerobic exercise group,and inhibitor group.Animal model of Aβ1-42-induced Alzheimer’s disease was made in each rat except for the sham operation group.In the sham operation group,2μL of normal saline was injected after cutting the dura mater.On the 3rd day after modeling,the inhibitor group was intraperitoneally injected with 2 mL of 50 mg/L AMPK Compound C,and the other groups were injected with the same amount of normal saline.After the injection,the rats in the aerobic exercise group and inhibitor group received 12 weeks of aerobic exercise training,and those in the sham operation group and model group received no treatment.After exercise,the changes in the spatial learning and memory ability of the rats were detected by water maze test and step down test;laser speckle imaging,hematoxylin-eosin staining,ELISA,and immunofluorescence were used to detect the changes in cerebral cortex blood flow,cerebral infarction volume,neuronal damage in brain tissue,expression levels of interleukin 1β,interleukin 6,and tumor necrosis factorαin brain tissue,nuclear translocation of NF-κB;western blot assay was used to detect the expression levels of p-AMPK,p-eNOS and NF-κB proteins.RESULTS AND CONCLUSION:Compared with the sham operation group,the rats in the model group had significantly prolonged escape latency,reduced number of times passing throug
作者
曹海信
王小梅
Cao Haixin;Wang Xiaomei(Department of Physical Education,Xi’an Shiyou University,Xi’an 710065,Shaanxi Province,China;School of Physical Education,Yan’an University,Yan’an 716000,Shaanxi Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2021年第11期1675-1681,共7页
Chinese Journal of Tissue Engineering Research
基金
陕西省教育厅2018年度专项科学研究计划项目(18jk0878),项目负责人:王小梅。
关键词
有氧运动
阿尔茨海默病
大脑
凋亡
模型
鼠
aerobic exercise
Alzheimer’s disease
brain
apoptosis
model
rat
