Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway.
Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway.
复制标题
烟酰胺单核苷酸通过激活Nrf2/HO-1信号通路减轻脑出血后脑损伤
DOI：
10.1038/s41598-017-00851-z
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发表时间：
2017-04-06
影响因子：
4.6
通讯作者：
Miao CY
中科院分区：
文献类型：
--
作者：
Wei CC;Kong YY;Li GQ;Guan YF;Wang P;Miao CY
补充NAD +已被证明可预防脑部疾病，如肌萎缩侧索硬化症和缺血性中风。然而，这种干预措施对脑出血（ICH）是否具有治疗效果尚不清楚。在本研究中，我们试图确定补充NAD +在ICH中的潜在治疗价值。在胶原酶诱导的脑出血（cICH）小鼠模型中，烟酰胺单核苷酸（NMN）——烟酰胺腺嘌呤二核苷酸（NAD +）生物合成的关键中间产物，在cICH发生30分钟后通过尾静脉给药以补充NAD +。NMN治疗并未减少血肿体积和血红蛋白含量。然而，NMN治疗显著减轻了脑出血区域的脑水肿、脑细胞死亡、氧化应激、神经炎症、细胞间黏附分子 - 1表达、小胶质细胞活化以及中性粒细胞浸润。从机制上讲，NMN增强了两种细胞保护蛋白的表达：血红素加氧酶1（HO - 1）和核因子E2相关因子2（Nrf2）。此外，NMN增加了Nrf2的核转位以使其活化。最后，持续7天的NMN治疗显著促进了体重和神经功能的恢复。这些结果表明，NMN通过抑制神经炎症/氧化应激来治疗ICH中的脑损伤。Nrf2/HO - 1信号通路的激活可能有助于NMN在ICH中的神经保护作用。
Replenishment of NAD+has been shown to protect against brain disorders such as amyotrophic lateral sclerosis and ischemic stroke. However, whether this intervention has therapeutic effects in intracerebral hemorrhage (ICH) is unknown. In this study, we sought to determine the potential therapeutic value of replenishment of NAD+in ICH. In a collagenase-induced ICH (cICH) mouse model, nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis, was administrated at 30 minutes post cICH from tail vein to replenish NAD+. NMN treatment did not decrease hematoma volume and hemoglobin content. However, NMN treatment significantly reduced brain edema, brain cell death, oxidative stress, neuroinflammation, intercellular adhesion molecule-1 expression, microglia activation and neutrophil infiltration in brain hemorrhagic area. Mechanistically, NMN enhanced the expression of two cytoprotective proteins: heme oxygenase 1 (HO-1) and nuclear factor-like 2 (Nrf2). Moreover, NMN increased the nuclear translocation of Nrf2 for its activation. Finally, a prolonged NMN treatment for 7 days markedly promoted the recovery of body weight and neurological function. These results demonstrate that NMN treats brain injury in ICH by suppressing neuroinflammation/oxidative stress. The activation of Nrf2/HO-1 signaling pathway may contribute to the neuroprotection of NMN in ICH.