Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion‐Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression

作者：Bailiu Ya, Qian Liu, Hongfang Li, Hongju Cheng, Ting Yu, Lin Chen, You Wang, Lili Yuan, Wenjuan Li, Wenyan Liu, Bo Bai · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2018 · DOI：10.1155/2018/6069150 · 被引用次数：114 · 研究领域：Genomics, phytochemicals, and oxidative stress、Neuroinflammation and Neurodegeneration Mechanisms、Neurogenesis and neuroplasticity mechanisms

The aim of this study was to investigate whether uric acid (UA) might exert neuroprotection via activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and regulating neurotrophic factors in the cerebral cortices after transient focal cerebral ischemia/reperfusion (FCI/R) in rats. UA was intravenously injected through the tail vein (16 mg/kg) 30 min after the onset of reperfusion in rats subjected to middle cerebral artery occlusion for 2 h. Neurological deficit score was performed to analyze neurological function at 24 h after reperfusion. Terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining and hematoxylin and eosin (HE) staining were used to detect histological injury of the cerebral cortex. Malondialdehyde (MDA), the carbonyl groups, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels were employed to evaluate oxidative stress. Nrf2 and its downstream antioxidant protein, heme oxygenase- (HO-) 1,were detected by western blot. Nrf2 DNA-binding activity was observed using an ELISA-based measurement. Expressions of BDNF and NGF were analyzed by immunohistochemistry. Our results showed that UA treatment significantly suppressed FCI/R-induced oxidative stress, accompanied by attenuating neuronal damage, which subsequently decreased the infarct volume and neurological deficit. Further, the treatment of UA activated Nrf2 signaling pathway and upregulated BDNF and NGF expression levels. Interestingly, the aforementioned effects of ...