肾动脉输注颞叶可预防羊革兰氏阴性败血症的髓质灌注不足、缺氧和急性肾损伤

IF 5.6 2区 医学 Q1 PHYSIOLOGY
Ashenafi H. Betrie, Shuai Ma, Connie P. C. Ow, Rachel M. Peiris, Roger G. Evans, Scott Ayton, Darius J. R. Lane, Adam Southon, Simon R. Bailey, Rinaldo Bellomo, Clive N. May, Yugeesh R. Lankadeva
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引用次数: 1

摘要

目的羊脓毒症急性肾损伤(AKI)发生前存在肾髓质灌注不足和缺氧。氧化/亚硝化应激、炎症和一氧化氮生成受损可能导致这种病理生理。我们测试了抗氧化和抗炎药物tempol是否可以改变这些反应。方法单侧肾切除术后,在肾皮质和肾髓质内置入肾动脉导管和激光多普勒/氧传感探头。未麻醉的绵羊静脉注射(IV)大肠杆菌,在脓毒症发作时静脉注射(IVT);30 mg kg−1 h−1),肾动脉颞叶(RAT;3mg kg−1h−1),或载体。结果脓毒症羊接受载药后出现肾髓质灌注不足(灌注减少76±16%)、缺氧(氧合减少70±13%)和AKI(肌酐清除率减少87±8%),在IVT期间变化相似。然而,RAT保留了髓质灌注(1072±307至1005±271单位),氧合(46±8至43±6 mmHg)和肌酐清除率(61±10至66±20 mL min−1)。血浆、肾髓质和皮质组织丙二醛和髓质3-硝基酪氨酸随脓毒症显著下降,但IVT或大鼠不受影响。与氧化/亚硝化应激标志物降低一致,皮质和髓核因子-红细胞相关因子-2显著升高,且不受IVT或RAT影响。然而,大鼠可阻止败血症诱导的皮质组织肿瘤坏死因子α (TNF-α;降低51±16%;p = 0.003)和内皮型一氧化氮合酶(eNOS;降低63±18%;p = 0.015)。结论在羊革兰氏阴性脓毒症中,肾动脉输注tempol可预防肾髓质灌注不足、缺氧和AKI,降低TNF-α表达和eNOS解偶联。然而,它不影响氧化/亚硝化应激标志物,革兰氏阴性脓毒症显著降低了氧化/亚硝化应激标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Renal arterial infusion of tempol prevents medullary hypoperfusion, hypoxia, and acute kidney injury in ovine Gram-negative sepsis

Aim

Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti-inflammatory drug, tempol, may modify these responses.

Methods

Following unilateral nephrectomy, we inserted renal arterial catheters and laser-Doppler/oxygen-sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg−1 h−1), renal arterial tempol (RAT; 3 mg kg−1 h−1), or vehicle.

Results

Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min−1). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3-nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor-erythroid-related factor-2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis-induced overexpression of cortical tissue tumor necrosis factor alpha (TNF-α; 51 ± 16% decrease; p = 0.003) and medullary Thr-495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015).

Conclusions

In ovine Gram-negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF-α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram-negative sepsis.

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来源期刊
Acta Physiologica
Acta Physiologica 医学-生理学
CiteScore
11.80
自引率
15.90%
发文量
182
审稿时长
4-8 weeks
期刊介绍: Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.
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