Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model
Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model
复制标题
褪黑激素在防止蛛网膜下腔出血模型中的早期脑损伤时激活 Nrf2-ARE 通路
DOI：
10.1111/j.1600-079x.2012.00978.x
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发表时间：
2012-09-01
影响因子：
10.3
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Wang, Zhong;Ma, Chao;Chen, Gang
褪黑激素通过调节实验性蛛网膜下腔出血（SAH）后的脑氧化应激对早期脑损伤（EBI）具有有益作用;然而，很少有研究涉及确切的潜在分子机制。迄今为止，褪黑激素与核因子红细胞2相关因子2和抗氧化反应元件（Nrf 2-ARE）通路之间的关系尚未在SAH模型中研究。本研究旨在探讨褪黑素对SAH大鼠Nrf 2-ARE通路的影响。成年雄性SD大鼠分为四组：（i）对照组（n = 18）;（ii）SAH组（n = 18）;（iii）SAH +媒介物组（n = 18）;和（iv）SAH +褪黑素组（n = 18）。大鼠SAH模型采用视交叉前池注入新鲜动脉血0.3mL，20 s内完成。在SAH +褪黑素组中，在SAH诱导后2和24小时，以150 mg/kg腹腔注射褪黑素。在SAH后48小时提取脑样品。褪黑激素治疗显著增加了Nrf 2-ARE通路相关因子的表达，如Nrf 2、血红素加氧酶-1、NAD（P）H：醌氧化还原酶1和谷胱甘肽S-转移酶a-1。SAH后给予褪黑激素可显著改善EBI，包括脑水肿、血脑屏障（BBB）损伤、皮质细胞凋亡和神经功能缺损。总之，在SAH模型中，SAH后给予褪黑激素可能通过激活Nrf 2-ARE通路并通过诱导抗氧化酶和解毒酶调节脑氧化应激来减轻EBI。
Melatonin has beneficial effects against early brain injury (EBI) by modulating cerebral oxidative stress after experimental subarachnoid hemorrhage (SAH); however, few investigations relate to the precise underlying molecular mechanisms. To date, the relation between melatonin and nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway has not been studied in SAH models. This study was undertaken to evaluate the influence of melatonin on Nrf2-ARE pathway in rats after SAH. Adult male SD rats were divided into four groups: (i) control group (n = 18); (ii) SAH group (n = 18); (iii) SAH + vehicle group (n = 18); and (iv) SAH + melatonin group (n = 18). The rat SAH model was induced by injection of 0.3 mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20 s. In SAH + melatonin group, melatonin was administered i.p. at 150 mg/kg at 2 and 24 hr after the induction of SAH. Brain samples were extracted at 48 hr after SAH. Treatment with melatonin markedly increased the expressions of Nrf2-ARE pathway-related agents, such as Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase a-1. Administration of melatonin following SAH significantly ameliorated EBI, including brain edema, bloodbrain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In conclusion, post-SAH melatonin 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.