Control of systemic inflammation through early nitric oxide supplementation with nitric oxide releasing nanoparticles.
Control of systemic inflammation through early nitric oxide supplementation with nitric oxide releasing nanoparticles.
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DOI：
10.1016/j.freeradbiomed.2020.09.025
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发表时间：
2020-12
影响因子：
7.4
通讯作者：
Cabrales P
中科院分区：
文献类型：
--
作者：
Williams AT;Muller CR;Govender K;Navati MS;Friedman AJ;Friedman JM;Cabrales P
改善脓毒症期间的免疫过度活动是恢复血液动力学、微血管血流和组织氧合以及预防多器官功能障碍综合征的关键。由脓毒症引起的全身炎症反应综合征最终导致内皮糖萼的降解和随后增加的血管渗漏。目前的液体复苏技术只能暂时改善脓毒症的结局，并可能导致水肿。一氧化氮（NO）治疗脓毒症在过去已经显示出希望，但是由于与递送相关的挑战和NO的瞬时性质，实施是困难的。为了解决这个问题，我们测试了使用静脉输注的NO释放纳米颗粒（NO-NP）持续递送外源性NO的抗炎功效。观察了NO-NP对内毒素血症小鼠微血流动力学和免疫功能的影响。NO-NP治疗通过促进M2巨噬细胞复极化显著减弱促炎反应，这减少了血清中促炎细胞因子的存在并减缓了血管外渗。总而言之，这导致NO-NP治疗动物的微血管血流量和72小时生存率显着改善。这项研究的结果表明，持续补充内源性NO可以改善和预防急性全身炎症的发病率。鉴于内皮功能障碍是许多急性炎症性疾病的共同特征，NO增强策略可能可用于治疗脓毒症和其他急性炎症性损伤，这些急性炎症性损伤引发严重的全身促炎反应并通常导致细胞因子风暴，如COVID-19中所见。
Amelioration of immune overactivity during sepsis is key to restoring hemodynamics, microvascular blood flow, and tissue oxygenation, and in preventing multi-organ dysfunction syndrome. The systemic inflammatory response syndrome that results from sepsis ultimately leads to degradation of the endothelial glycocalyx and subsequently increased vascular leakage. Current fluid resuscitation techniques only transiently improve outcomes in sepsis, and can cause edema. Nitric oxide (NO) treatment for sepsis has shown promise in the past, but implementation is difficult due to the challenges associated with delivery and the transient nature of NO. To address this, we tested the anti-inflammatory efficacy of sustained delivery of exogenous NO using i.v. infused NO releasing nanoparticles (NO-np). The impact of NO-np on microhemodynamics and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model was evaluated. NO-np treatment significantly attenuated the pro-inflammatory response by promoting M2 macrophage repolarization, which reduced the presence of pro-inflammatory cytokines in the serum and slowed vascular extravasation. Combined, this resulted in significantly improved microvascular blood flow and 72-h survival of animals treated with NO-np. The results from this study suggest that sustained supplementation of endogenous NO ameliorates and may prevent the morbidities of acute systemic inflammatory conditions. Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19.
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DOI：
10.1186/cc11236
发表时间：
2012-06-19
期刊：
Critical care (London, England)
影响因子：
--
作者：
Bezemer R;Bartels SA;Bakker J;Ince C
通讯作者：
Ince C
DOI：
10.1097/mbc.0000000000000602
发表时间：
2017-07
期刊：
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
影响因子：
--
作者：
Helms CC;Kapadia S;Gilmore AC;Lu Z;Basu S;Kim-Shapiro DB
通讯作者：
Kim-Shapiro DB
影响因子：
82.9
作者：
Kuba K;Imai Y;Rao S;Gao H;Guo F;Guan B;Huan Y;Yang P;Zhang Y;Deng W;Bao L;Zhang B;Liu G;Wang Z;Chappell M;Liu Y;Zheng D;Leibbrandt A;Wada T;Slutsky AS;Liu D;Qin C;Jiang C;Penninger JM
通讯作者：
Penninger JM
DOI：
10.1186/s13054-015-0741-z
发表时间：
2015-01-28
期刊：
Critical care (London, England)
影响因子：
--
作者：
Chelazzi C;Villa G;Mancinelli P;De Gaudio AR;Adembri C
通讯作者：
Adembri C
DOI：
10.1186/cc3753
发表时间：
2005
期刊：
Critical care (London, England)
影响因子：
--
作者：
Ince C
通讯作者：
Ince C