Curcumin plays neuroprotective roles against traumatic brain injury partly via Nrf2 signaling
Curcumin plays neuroprotective roles against traumatic brain injury partly via Nrf2 signaling
复制标题
姜黄素部分通过 Nrf2 信号传导对创伤性脑损伤发挥神经保护作用
DOI：
10.1016/j.taap.2018.03.020
复制
发表时间：
2018-05-01
影响因子：
3.8
通讯作者：
Zhao, Rui
中科院分区：
文献类型：
--
作者：
Dong, Wenwen;Yang, Bei;Zhao, Rui
创伤性脑损伤（Traumatic brain injury，TBI）是一个严重的公共卫生问题，目前尚无有效的治疗方法。姜黄素已被证明是有益的神经保护在体内和体外，但其潜在的机制仍不清楚。这项研究确定了姜黄素在小鼠TBI中的神经保护作用是否依赖于NF-E2相关因子（Nrf 2）通路。使用Feeney重物跌落挫伤模型来模拟TBI。TBI诱导后15 min腹腔内给予姜黄素，并在TBI后24 h收集脑。采用Western blot和qRT-PCR检测脑损伤后24 h Nrf 2及其下游基因（Hmox-1、Nqo 1、Gclm和Gclc）的表达。此外，在野生型（W7）和Nrf 2敲除（Nrf 2-KO）小鼠中评估水肿、氧化损伤、细胞凋亡和炎症反应，以探索姜黄素处理后Nrf 2信号传导的作用。在野生型小鼠中，姜黄素治疗导致同侧皮质损伤、中性粒细胞浸润和小胶质细胞活化减少，从而改善神经元存活以对抗TBI诱导的细胞凋亡和变性。这些作用伴随着Nrf 2的表达和核转位增加，以及抗氧化酶的表达增强。然而，Nrf 2缺失减弱了姜黄素在TBI后Nrf 2-KO小鼠中的神经保护作用。这些发现表明，姜黄素对TBI的影响与Nrf 2通路的激活有关，为Nrf 2的神经保护作用和姜黄素对TBI的潜在治疗用途提供了新的见解。
Traumatic brain injury (TBI), which leads to high mortality and morbidity, is a prominent public health problem worldwide with no effective treatment. Curcumin has been shown to be beneficial for neuroprotection in vivo and in vitro, but the underlying mechanism remains unclear. This study determined whether the neuroprotective role of curcumin in mouse TBI is dependent on the NF-E2-related factor (Nrf2) pathway. The Feeney weight-drop contusion model was used to mimic TBI. Curcumin was administered intraperitoneally 15 min after TBI induction, and brains were collected at 24 h after TBI. The levels of Nrf2 and its downstream genes (Hmox-1, Nqo1, Gclm, and Gclc) were detected by Western blot and qRT-PCR at 24 h after TBI. In addition, edema, oxidative damage, cell apoptosis and inflammatory reactions were evaluated in wild type (W7) and Nrf2-knockout (Nrf2-KO) mice to explore the role of Nrf2 signaling after curcumin treatment. In wild type mice, curcumin treatment resulted in reduced ipsilateral cortex injury, neutrophil infiltration, and microglia activation, improving neuron survival against TBI-induced apoptosis and degeneration. These effects were accompanied by increased expression and nuclear translocation of Nrf2, and enhanced expression of antioxidant enzymes. However, Nrf2 deletion attenuated the neuroprotective effects of curcumin in Nrf2-KO mice after TBI. These findings demonstrated that curcumin effects on TBI are associated with the activation the Nrf2 pathway, providing novel insights into the neuroprotective role of Nrf2 and the potential therapeutic use of curcumin for TBI.