Combination of NAD+ and NADPH Offers Greater Neuroprotection in Ischemic Stroke Models by Relieving Metabolic Stress
Combination of NAD+ and NADPH Offers Greater Neuroprotection in Ischemic Stroke Models by Relieving Metabolic Stress
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NAD( ) 和 NADPH 的组合通过缓解代谢应激为缺血性中风模型提供更好的神经保护
DOI：
10.1007/s12035-017-0809-7
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发表时间：
2018-07-01
影响因子：
5.1
通讯作者：
Qin, Zheng-Hong
中科院分区：
文献类型：
--
作者：
Huang, Qiao;Sun, Meiling;Qin, Zheng-Hong
据报道，还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）和β-烟酰胺腺嘌呤二核苷酸水合物（NAD（+））均对缺血性神经元损伤具有有效的神经保护作用。NADPH和NAD（+）都是抗氧化和细胞能量代谢的重要辅助因子。我们研究了NADPH和NAD（+）联合应用是否能对缺血性卒中的细胞和动物模型提供更好的神经保护作用。原代培养神经元的体外研究表明，在复氧早期给予NAD（+）可有效保护神经元免受氧-葡萄糖剥夺/复氧（OGD/R）损伤。小鼠体内研究也表明，NAD（+）在再灌注后2小时内给药可有效改善缺血性脑损伤。NADPH和NAD（+）的组合不仅提供了更大的有益效果，而且在中风的细胞和动物模型中提供了更大的治疗窗口。NADPH和NAD（+）联合作用可显著增加三磷酸腺苷（ATP）水平，降低活性氧（ROS）水平和大分子氧化损伤。此外，联合用药显着降低了长期死亡率，改善了功能恢复，并抑制了缺血性中风后参与细胞凋亡和坏死性凋亡的信号通路。目前的研究表明，NAD（+）和NADPH的组合可以在较小的NADPH剂量下产生更大的治疗效果;另一方面，NADPH可以显著延长NAD（+）的治疗窗口。目前的研究结果表明，NADPH和NAD（+）的组合可能为缺血性卒中提供一种新的有效治疗方法。
Both reduced nicotinamide adenine dinucleotide phosphate (NADPH) and beta-nicotinamide adenine dinucleotide hydrate (NAD(+)) have been reported to have potent neuroprotective effects against ischemic neuronal injury. Both NADPH and NAD(+) are essential cofactors for anti-oxidation and cellular energy metabolism. We investigated if combined NADPH and NAD(+) could offer better neuroprotective effects on cellular and animal models of ischemic stroke. In vitro studies with primary cultured neurons demonstrated that NAD(+) was effective in protecting neurons against oxygen-glucose deprivation/reoxygenation (OGD/R) injury when given during the early time period of reoxygenation. In vivo studies in mice also suggested that NAD(+) was effective for ameliorating ischemic brain damage when administered within 2 h after reperfusion. The combination of NADPH and NAD(+) provided not only greater beneficial effects but also larger therapeutic window in both cellular and animal models of stroke. The combination of NADPH and NAD(+) significantly increased the levels of adenosine triphosphate (ATP) and reduced the levels of reactive oxygen species (ROS) and oxidative damage of macromolecules. Furthermore, the combined medication significantly reduced long-term mortality, improved the functional recovery, and inhibited signaling pathways involved in apoptosis and necroptosis after ischemic stroke. The present study indicates that the combination of NAD(+) and NADPH can produce greater therapeutic effects with smaller dose of NADPH; on the other hand, NADPH can significantly prolong the therapeutic window of NAD(+). The current results suggest that the combination of NADPH and NAD(+) may provide a novel effective therapy for ischemic stroke.