Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.
Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.
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DOI：
10.1038/ki.2011.347
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发表时间：
2012-02
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
脓毒症期间发生急性肾损伤的患者的死亡率几乎翻了一番。治疗的有效性受到阻碍，因为它通常是在症状发作后才开始的。由于脓毒症期间的肾微血管衰竭与活性氮物质的产生相关，因此使用脓毒症诱导的急性肾损伤的盲肠结扎和穿刺（CLP）小鼠模型研究了白藜芦醇（一种也能够清除活性氮物质的多酚血管扩张剂）的治疗潜力。白藜芦醇在CLP后5.5小时给药时逆转了皮质毛细血管灌注的下降，通过活体显微镜评估，在6小时以剂量依赖性方式。白藜芦醇在毛细血管灌注方面产生了最大的改善，并增加了肾血流量和肾小球滤过率，而不增加全身压力。CLP后6 h单次给药无法改善18 h评估的肾微循环;然而，12 h第二次给药显著改善微循环，降低肾小管中活性氮水平，同时改善肾功能。此外，在6、12和18小时给予白藜芦醇显著提高了存活率。因此，白藜芦醇可能具有双重作用机制，以恢复肾微循环和抑制活性氮，从而保护肾小管上皮细胞，即使在脓毒症发作后给药。
The mortality rate of patients who develop acute kidney injury during sepsis nearly doubles. The effectiveness of therapy is hampered because it is usually initiated only after the onset of symptoms. As renal microvascular failure during sepsis is correlated with the generation of reactive nitrogen species, the therapeutic potential of resveratrol, a polyphenol vasodilator that is also capable of scavenging reactive nitrogen species, was investigated using the cecal ligation and puncture (CLP) murine model of sepsis-induced acute kidney injury. Resveratrol when given at 5.5 h following CLP reversed the decline in cortical capillary perfusion, assessed by intravital microscopy, at 6 h in a dose-dependent manner. Resveratrol produced the greatest improvement in capillary perfusion and increased renal blood flow and the glomerular filtration rate without raising systemic pressure. A single dose at 6 h after CLP was unable to improve renal microcirculation assessed at 18 h; however, a second dose at 12 h significantly improved microcirculation and decreased the levels of reactive nitrogen species in tubules, while improving renal function. Moreover, resveratrol given at 6, 12, and 18 h significantly improved survival. Hence, resveratrol may have a dual mechanism of action to restore the renal microcirculation and scavenge reactive nitrogen species, thus protecting the tubular epithelium even when administered after the onset of sepsis.
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影响因子：
7.3
作者：
Hoshino J;Park EJ;Kondratyuk TP;Marler L;Pezzuto JM;van Breemen RB;Mo S;Li Y;Cushman M
通讯作者：
Cushman M
败血症微血管内皮的炎症反应：氧化剂的作用。
影响因子：
2.4
作者：
Cepinskas, Gediminas;Wilson, John X.
通讯作者：
Wilson, John X.
DOI：
10.1124/jpet.102.033340
发表时间：
2002-07-01
影响因子：
3.5
作者：
Marier, JF;Vachon, P;Ducharme, MP
通讯作者：
Ducharme, MP
影响因子：
13.6
作者：
Doi, Kent;Yuen, Peter S. T.;Star, Robert A.
通讯作者：
Star, Robert A.
影响因子：
3.9
作者：
Chung, Sangwoon;Yao, Hongwei;Caito, Samuel;Hwang, Jae-Woong;Arunachalam, Gnanapragasam;Rahman, Irfan
通讯作者：
Rahman, Irfan