Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis.
Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis.
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DOI：
10.1016/j.freeradbiomed.2018.05.073
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发表时间：
2018-08-01
影响因子：
7.4
通讯作者：
Peng T
中科院分区：
文献类型：
--
作者：
Hong G;Zheng D;Zhang L;Ni R;Wang G;Fan GC;Lu Z;Peng T
脓毒症引起的多器官衰竭仍然是重症监护病房发病率和死亡率的主要原因。烟酰胺核苷(NR)是烟酰胺腺嘌呤二核苷酸(NAD+)的前体，在调节氧化应激中起重要作用。本研究调查了给予NR是否能预防脓毒症时的氧化应激和器官损伤。通过注射脂多糖或粪便注射建立小鼠脓毒症模型。在脓毒症发作前给予NR。培养的巨噬细胞和血管内皮细胞与不同的试剂孵育。在脓毒症模型中，NR可提高NAD+水平，降低肺和心脏组织的氧化应激、炎症反应和caspase-3活性，这与肺微血管通透性降低和心肌功能障碍有关，从而降低死亡率。NR的这些保护作用与降低脓毒症小鼠血浆高迁移率族蛋白-1(HMGB1)水平有关。用NR预先处理巨噬细胞后，巨噬细胞在内毒素刺激下NAD+含量增加，HMGB1释放减少。NR还可抑制由内毒素处理的巨噬细胞条件培养液诱导的内皮细胞的ROS生成和细胞凋亡。此外，EX527对SIRT1的抑制作用抵消了NR对巨噬细胞释放HMGB1、内皮细胞ROS和细胞凋亡的负面影响。给予NR可预防肺和心脏损伤，并提高脓毒症患者的存活率，其机制可能是通过NAD+/SIRT1信号通路抑制HMGB1的释放和氧化应激。鉴于NR已被用作健康补充剂，它可能是预防脓毒症器官损伤的有用药剂。
Sepsis-caused multiple organ failure remains the major cause of morbidity and mortality in intensive care units. Nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+), which is important in regulating oxidative stress. This study investigated whether administration of NR prevented oxidative stress and organ injury in sepsis. Mouse sepsis models were induced by injection of lipopolysaccharides (LPS) or feces-injection-inperitoneum. NR was given before sepsis onset. Cultured macrophages and endothelial cells were incubated with various agents. Administration of NR elevated the NAD+ levels, and elicited a reduction of oxidative stress, in-flammation and caspase-3 activity in lung and heart tissues, which correlated with attenuation of pulmonary microvascular permeability and myocardial dysfunction, leading to less mortality in sepsis models. These protective effects of NR were associated with decreased levels of plasma high mobility group box-1 (HMGB1) in septic mice. Consistently, pre-treatment of macrophages with NR increased NAD+ content and reduced HMGB1 release upon LPS stimulation. NR also prevented reactive oxygen species (ROS) production and apoptosis in endothelial cells induced by a conditioned-medium collected from LPS-treated macrophages. Furthermore, inhibition of SIRT1 by EX527 offset the negative effects of NR on HMGB1 release in macrophages, and ROS and apoptosis in endothelial cells. Administration of NR prevents lung and heart injury, and improves the survival in sepsis, likely by inhibiting HMGB1 release and oxidative stress via the NAD+/SIRT1 signaling. Given NR has been used as a health supplement, it may be a useful agent to prevent organ injury in sepsis.
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capn4 的缺失可通过防止 ATP 合酶破坏和抑制线粒体超氧化物生成来保护心脏免受内毒素损伤。
DOI：
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发表时间：
2015-09
期刊：
Circulation. Heart failure
影响因子：
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作者：
Ni R;Zheng D;Wang Q;Yu Y;Chen R;Sun T;Wang W;Fan GC;Greer PA;Gardiner RB;Peng T
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发表时间：
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期刊：
Diabetes, obesity & metabolism
影响因子：
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DOI：
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发表时间：
2013-10-20
期刊：
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影响因子：
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作者：
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