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

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 experiments were divided into 4 groupd: Sham group, HIE group, Sham + Nrf2 group, and HIE + Nrf2group, with 10 neonatal SD rats in each group. The HIE model was established, and unloaded adenovirus or adenovirus containing Nrf2 overexpression vector was transfused into the ventricle. After 14days, 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-1β ( IL-1β), interleukin-6 (IL-6), and interleukin-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 molecule-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 staining. 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, thevolume of cerebral infarction in the HIE + Nrf2 group was significantly decreased, neuronal nucleus shrinkage was decreased, the levels of TNF-α, IL-1β and IL-6 in brain tissues were significantly decreased, 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 significantly down-regulated, the expression levels of Arg-1, CD206, Nrf2, BDNF and GDNF were significantly up-regulated (P < 0. 05). Conclusion Nrf2 can reduce neuroinflammation by promotingthe transformation of microglia from M1 type to M2 type to improve the brain injury of neonatal rats with HIE.

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