Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway
Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway
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DOI：
10.1080/13880209.2018.1502326
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发表时间：
2018-11-21
影响因子：
3.8
通讯作者：
Feng, Juan
中科院分区：
文献类型：
--
作者：
Gao, Yan;Fu, Rongrong;Feng, Juan
背景：缺氧缺血性脑病（HIE）具有较高的发病率和死亡率。白藜芦醇具有多种生物学特性，包括抗氧化、抗炎和神经保护作用。
目的：本实验通过调节新生大鼠的Nrf2/HO - 1通路，研究白藜芦醇（RESV）对HIE的神经保护功效。
材料和方法：将7日龄幼鼠（n = 48）分为四组。第一组大鼠接受2%二甲基亚砜生理盐水（假手术组），第二组大鼠进行单侧颈动脉结扎并缺氧（92%氮气和8%氧气）2.5小时（缺氧缺血；HI），第三组和第四组大鼠分别在HI诱导前7天通过腹腔注射（ip）接受20（RESV 20 + HI）或40mg/kg（RESV 40 + HI；第四组）的RESV。
结果：用RESV（20或40）预处理显著降低（p < 0.01）脑水肿（86.23% - 71.26%或65.24%）、梗死面积（33.85% - 19.81%或14.30%）、脂质过氧化产物、炎症标志物[白细胞介素 - 1β 186 - 110或82；白细胞介素 - 6 255 - 146或103；肿瘤坏死因子 - α 310 - 204或137；核因子 - κB 205 - 115或91（p65亚基）]，并通过增强谷胱甘肽过氧化物酶（GPx）5.22 - 6.49或7.78、过氧化氢酶（CAT）51 - 55或59、超氧化物歧化酶（SOD）2.5 - 3.05或3.25的活性显著恢复（p < 0.01）抗氧化状态；通过显著上调（p < 0.01）血红素加氧酶1（HO - 1）0.65 - 0.69或0.73以及核因子红细胞2相关因子2（Nrf2）0.73 - 0.86或0.91。
讨论与结论：RESV通过上调Nrf2和HO - 1信号通路的蛋白表达，从而减轻HI诱导的新生大鼠的氧化应激和炎症反应，显示出其神经治疗潜力。
Context: Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities.Objective: The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats.Materials and methods: Seven-day-old pups (n=48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N-2 and 8% O-2) for 2.5 h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20 + HI) or 40 mg/kg (RESV 40 + HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7 days prior to HI induction.Results: Pre-treatment with RESV (20 or 40) markedly reduced (p < 0.01) the cerebral oedema (86.23-71.26 or 65.24%), infarct area (33.85-19.81 or 14.30%), lipid peroxidation products, inflammatory markers [IL-1 beta 186-110 or 82; IL-6 255-146 or 103; TNF-alpha 310-204 or 137; NF-kappa B 205-115 or 91) p65 subunit] and significantly restored (p < 0.01) the antioxidative status by enhancing the activities of glutathione peroxidase (GPx) 5.22-6.49 or 7.78; catalase (CAT) 51-55 or 59, superoxide dismutase (SOD) 2.5-3.05 or 3.25; through marked upregulation (p < 0.01) of heme oxygenase 1 (HO-1) 0.65-0.69 or 0.73; and nuclear factor erythroid 2 related factor 2 (Nrf2) 0.73-0.86 or 0.91.Discussion and Conclusions: RESV displays its neurotherapeutic potential via upregulating the protein expression of Nrf2 and HO-1 signalling pathway and thereby attenuates oxidative stress and inflammatory response in HI-induced neonatal rats.