Recombinant human erythropoietin (rhEPO) alleviates early brain injury following subarachnoid hemorrhage in rats: Possible involvement of Nrf2-ARE pathway
Recombinant human erythropoietin (rhEPO) alleviates early brain injury following subarachnoid hemorrhage in rats: Possible involvement of Nrf2-ARE pathway
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重组人促红细胞生成素（rhEPO）减轻大鼠蛛网膜下腔出血后的早期脑损伤：可能涉及 Nrf2-ARE 通路
DOI：
10.1016/j.cyto.2010.08.011
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发表时间：
2010-12-01
期刊：
影响因子：
3.8
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Zhang, Jian;Zhu, Yun;Chen, Gang
重组人促红细胞生成素（rhEPO）对蛛网膜下腔出血（SAH）晚期血管痉挛和脑损伤有有益作用；然而，关于rhEPO在sah诱导的早期脑损伤（EBI）中的作用的研究很少，其潜在机制也尚不清楚。本研究旨在探讨rhEPO对SAH大鼠核因子-红细胞2相关因子2和抗氧化反应因子（Nrf2-ARE）通路及早期脑损伤的影响。将成年雄性SD大鼠分为4组：(1)对照组（n = 18）；(2) SAH组（18例）；(3) SAH +车辆组（n = 18）；(4) SAH + rhEPO组（18例）。将新鲜动脉非肝素化血0.3 ml注入交叉前池，20s后建立大鼠SAH模型。在SAH + rhEPO组，在SAH诱导后5分钟开始以1000 U/kg滴注rhEPO，每8 h重复一次，持续48 h。在SAH后48 h提取脑样本。结果，我们发现rhEPO治疗显著增加Nrf2- are通路相关因子的表达，如Nrf2、血红素氧化酶-1 （HO-1）、NAD(P)H：醌氧化还原酶-1 （NQO1）和谷胱甘肽s -转移酶α -1 （gst - α 1）。SAH后给予rhEPO可显著改善EBI，如皮质细胞凋亡、脑水肿和血脑屏障（BBB）损伤。综上所述，SAH后给药rhEPO可能通过激活Nrf2-ARE通路，诱导抗氧化和解毒酶调节脑氧化应激，从而减轻SAH模型中的EBI。(C) 2010 Elsevier Ltd.版权所有。
Recombinant human erythropoietin (rhEPO) has demonstrated beneficial effects against vasospasm and brain damage at the late stage of subarachnoid hemorrhage (SAH); however few investigations have been done about the effect of rhEPO on SAH-induced early brain injury (EBI) and also the underlying mechanisms remain unclear. This study was undertaken to evaluate the influence of rhEPO on the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway and early brain injury in rats after SAH. Adult male SD rats were divided into four groups: (1) control group (n = 18); (2) SAH group (n = 18); (3) SAH + vehicle group (n = 18); and (4) SAH + rhEPO group (n = 18). The rat SAH model was induced by injection of 0.3 ml fresh arterial, non-heparinized blood into the prechiasmatic cistern in 20s. In SAH + rhEPO group, rhEPO was administered i.p. at 1000 U/kg starting 5 min after the induction of SAH and repeated every 8 h for 48 h. Brain samples were extracted at 48 h after SAH. As a result, we found that treatment with rhEPO markedly increased expressions of Nrf2-ARE pathway related agents, such as Nrf2, heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO1), and glutathione S-transferase alpha-1 (GST-alpha 1). Administration of rhEPO following SAH significantly ameliorated EBI, such as cortical apoptosis, brain edema, and blood-brain barrier (BBB) impairment. In conclusion, post-SAH rhEPO administration may attenuate EBI in this SAH model, possibly through activating Nrf2-ARE pathway and modulating cerebral oxidative stress by inducing antioxidant and detoxifying enzymes. (C) 2010 Elsevier Ltd. All rights reserved.