Modulation of oxidative and nitrosative stress attenuates microvascular hyperpermeability in ovine model of Pseudomonas aeruginosa sepsis.
Modulation of oxidative and nitrosative stress attenuates microvascular hyperpermeability in ovine model of Pseudomonas aeruginosa sepsis.
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DOI：
10.1038/s41598-021-03320-w
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发表时间：
2021-12-14
影响因子：
4.6
通讯作者：
Enkhbaatar P
中科院分区：
文献类型：
--
作者：
Fukuda S;Niimi Y;Hirasawa Y;Manyeza ER;Garner CE;Southan G;Salzman AL;Prough DS;Enkhbaatar P
在脓毒症中，氧化/亚硝化应激（O&NS）引起的微血管高通透性在组织水肿中起重要作用，导致多器官功能障碍和死亡率增加。我们假设一种新的化合物R-107，一种O&NS调节剂，在羊脓毒症模型中有效地改善微血管高通透性的严重程度并保持多器官功能。用铜绿假单胞菌（PA） （1 × 1010 CFUs）静脉滴注22只成年美利奴母羊致脓毒症。各组动物分为：1)对照组（n = 13）：肌肉注射生理盐水；2)处理（n = 9）： 50 mg/kg R-107 IM。注射PA后给予治疗，监测24 h。与对照组相比，R-107处理显著降低了液体需水量（15-24 h, P < 0.05）、净液体平衡（9-24 h, P < 0.05）和肺/心/肾含水量（P = 0.02/0.04/0.01）。R-107处理显著降低24 h肺损伤评分/改良羊SOFA评分（P = 0.01/0.04），显著降低血浆动脉乳酸（21-24 h, P < 0.05）、shed syndecan-1 （3-6 h, P < 0.05）、白细胞介素-6 （6-12 h, P < 0.05）水平，显著降低肺组织3-硝基酪氨酸和血管内皮生长因子- a表达（P = 0.03/0.002）。R-107治疗无不良反应。综上所述，R-107对O&NS的调节可降低高透性标志物，改善多器官功能。
In sepsis, microvascular hyperpermeability caused by oxidative/nitrosative stress (O&NS) plays an important role in tissue edema leading to multi-organ dysfunctions and increased mortality. We hypothesized that a novel compound R-107, a modulator of O&NS, effectively ameliorates the severity of microvascular hyperpermeability and preserves multi-organ function in ovine sepsis model. Sepsis was induced in twenty-two adult female Merino sheep by intravenous infusion of Pseudomonas aeruginosa (PA) (1 × 1010 CFUs). The animals were allocated into: 1) Control (n = 13): intramuscular injection (IM) of saline; and 2) Treatment (n = 9): IM of 50 mg/kg R-107. The treatment was given after the PA injection, and monitored for 24-h. R-107 treatment significantly reduced fluid requirement (15–24 h, P < 0.05), net fluid balance (9–24 h, P < 0.05), and water content in lung/heart/kidney (P = 0.02/0.04/0.01) compared to control. R-107 treatment significantly decreased lung injury score/modified sheep SOFA score at 24-h (P = 0.01/0.04), significantly lowered arterial lactate (21–24 h, P < 0.05), shed syndecan-1 (3–6 h, P < 0.05), interleukin-6 (6–12 h, P < 0.05) levels in plasma, and significantly attenuated lung tissue 3-nitrotyrosine and vascular endothelial growth factor-A expressions (P = 0.03/0.002) compared to control. There was no adverse effect in R-107 treatment. In conclusion, modulation of O&NS by R-107 reduced hyperpermeability markers and improved multi-organ function.
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影响因子：
3.2
作者：
Lee, Warren L.;Liles, W. Conrad
通讯作者：
Liles, W. Conrad
影响因子：
3.1
作者：
Huet, Olivier;Dupic, Laurent;Duranteau, Jacques
通讯作者：
Duranteau, Jacques
影响因子：
56.3
作者：
Cohen, Jonathan;Vincent, Jean-Louis;Pelfrene, Eric
通讯作者：
Pelfrene, Eric
影响因子：
2.9
作者：
Brandenburg, Kenneth S.;Calderon, Diego F.;Czuprynski, Charles J.
通讯作者：
Czuprynski, Charles J.
影响因子：
8.8
作者：
López, A;Lorente, JA;Grover, R
通讯作者：
Grover, R