Activation of Nrf2-ARE pathway in brain after traumatic brain injury
Activation of Nrf2-ARE pathway in brain after traumatic brain injury
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DOI：
10.1016/j.neulet.2007.11.060
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发表时间：
2008-01-31
影响因子：
2.5
通讯作者：
Yin, Hong-Xia
中科院分区：
文献类型：
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作者：
Yan, Wei;Wang, Han-Dong;Yin, Hong-Xia
继发性脑损伤对创伤性脑损伤患者的预后起着至关重要的作用。继发性脑损伤的机制复杂且相互关联。以前的研究集中在其中一种机制上，已被证明在临床实践中无效。因此，需要一种能够中断脑损伤背后的多种机制的靶点。NRF2-ARE途径已被证明是减少氧化应激、炎性损伤和有毒代谢物积累的关键调节因子，这些都参与了脑损伤的发生。然而，颅脑损伤后Nrf2-ARE通路是否被激活尚无研究。本研究采用Western印迹法检测脑挫伤后24 h核内Nrf2蛋白水平，并用逆转录聚合酶链式反应(RT-PCR)检测Nrf2调控基因产物血红素加氧酶-1(HO-1)和NAD(P)H：Quone氧化还原酶-1(NQO1)的基因表达水平。此外，我们还利用免疫组织化学方法对Nrf2和HO-I的表达进行了定位。脑损伤后，核内Nrf2蛋白水平显著升高，HO-1和NQO1mRNA水平均上调。此外，Nrf2和HO-1均定位于相同类型的细胞。根据这些结果，可以推测脑损伤后Nrf2-ARE通路被激活。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
Secondary brain injury plays a pivotal role in the outcome of patients suffering from traumatic brain injury (TBI). The mechanisms underlying secondary brain injury are complex and interrelated. Previous studies focused on one of these mechanisms have been proved to be ineffective in clinical practice. Therefore, a target, which can interrupt multi-mechanisms underlying TBI, is desirable. Nrf2-ARE pathway has been proved to be the key regulator in reducing oxidative stress, inflammatory damage and accumulation of toxic metabolites, which are all involved in TBI. However, whether Nrf2-ARE pathway is activated after TBI has not been studied. In the present study, the nuclear Nrf2 protein level was detected by Western blot, and the mRNA levels of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1), two Nrf2-regulated gene products, were determined using reverse-transcriptase polymerase chain reaction (RT-PCR) 24 It after TBI. Furthermore, we also localized the expression of Nrf2 and HO-I using immunohistochemical study. After TBI, the nuclear Nrf2 protein level was significantly increased, and the mRNA levels of both HO-1 and NQO1 were also up regulated. Moreover, both Nrf2 and HO-1 were localized in the same types of cells. According to these results, it could be postulated that Nrf2-ARE pathway was activated in brain after TBI. (c) 2007 Elsevier Ireland Ltd. All rights reserved.