医学分子生物学杂志2025，Vol.22Issue(3)：229-236,8.DOI:10.3870/j.issn.1672-8009.2025.03.004
Nrf2对新生缺氧缺血性脑病大鼠脑损伤和小胶质细胞极化的影响
Effect of Nrf2 on Brain Injury and Microglial Cell Polarization in Neonatal Hypoxic-ischemic Encephalopathy Rats
摘要
Abstract
Objective To investigate the effect of nuclear factor E2-associated factor 2(Nrf2)on brain injury in neonatal hypoxic-ischemic encephalopathy(HIE)rats.Methods The experi-ments were divided into 4 groupd:Sham group,HIE group,Sham+Nrf2 group,and HIE+Nrf2 group,with 10 neonatal SD rats in each group.The HIE model was established,and unloaded ade-novirus or adenovirus containing Nrf2 overexpression vector was transfused into the ventricle.After 14 days,cerebral infarction was detected by 2,3,5 triphenyltetrazolium chloride(TTC)staining,and brain histopathological changes were observed by Hematoxylin-eosin(HE)staining.The levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β),interleukin-6(IL-6),and inter-leukin-10(IL-10)in brain tissues were determined by enzyme-linked immunosorbent assay(ELISA).The proportion of M1-type microglia labeled with ionized calcium binding adaptor mole-cule-1(Iba-1)/inducible nitric oxide synthetase(iNOS)and the proportion of M2-type microglia labeled with Iba-1/arginase 1(Arg-1)were detected by double-labeling immunofluorescence stai-ning.The protein expression levels of iNOS,CD86,Arg-1,Macrophage mannose receptor(CD206),Nrf2,brain-derived neurotrophic factor(BDNF),and glia-derived neurotrophic factor(GDNF)were detected by Western blotting.Results Compared with those in the HIE group,the volume of cerebral infarction in the HIE+Nrf2 group was significantly decreased,neuronal nucleus shrinkage was decreased,the levels of TNF-α,IL-1 β and IL-6 in brain tissues were significantly de-creased,and the levels of IL-10 were significantly increased,the proportion of Iba-1+/iNOS+M1-type microglia was significantly decreased,and the proportion of Iba-1+/Arg-1+M2-type microglia was significantly increased,the expression levels of iNOS and CD86 protein in brain tissues were sig-nificantly down-regulated,the expression levels of Arg-1,CD206,Nrf2,BDNF and GDNF were sig-nificantly up-regulated(P＜0.05).Conclusion Nrf2 can reduce neuroinflammation by promoting the transformation of microglia from M1 type to M2 type to improve the brain injury of neonatal rats with HIE.关键词
缺氧缺血性脑病/核因子-E2相关因子2/小胶质细胞极化/炎症Key words
hypoxic-ischemic encephalopathy/nuclear factor erythroid 2 related factor 2/mi-croglia polarization/inflammation分类
临床医学引用本文复制引用
吴秩珊,肖珮,李艳良,余占章..Nrf2对新生缺氧缺血性脑病大鼠脑损伤和小胶质细胞极化的影响[J].医学分子生物学杂志,2025,22(3):229-236,8.基金项目
东莞市松山湖中心医院院内重大科研项目培育基金项目(No.SZR002) This work was supported by a grant from the Dongguan Songshan Lake Central Hospital Major Scientific Research Project Cultivation Fund Project(No.SZR002) （No.SZR002）
