Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney
Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney
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DOI：
10.1152/ajprenal.00334.2005
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发表时间：
2006-04-01
影响因子：
4.2
通讯作者：
Agarwal, A
中科院分区：
文献类型：
--
作者：
Basireddy, M;Isbell, TS;Agarwal, A
活性氧和活性氮在肾缺血再灌注（I/R）损伤的病理生理过程中起着重要作用。最近的研究表明，亚硝酸盐（NO2-）作为一种内源性来源的一氧化氮（NO），特别是在缺氧和酸中毒的存在。纳摩尔浓度的NO2-可减少体内肝脏和心脏I/R后的损伤。本研究旨在探讨NO_2-在肾I/R损伤中的作用。雄性Sprague-Dawley大鼠在异氟烷麻醉下进行单侧肾切除术，随后对侧肾缺血45分钟或假手术。在诱导缺血后22.5分钟或缺血前15分钟，动物接受生理盐水、NO2-钠或硝酸钠（NO3-; 1.2 nmol/ g体重ip）。另一组动物在缺血前45分钟接受生理盐水、NO2-或NO3-（0.12、1.2或12 nmol/ g体重iv）。I/R损伤后血清肌酐和血尿素氮升高，但在急性肾损伤后24和48 h，治疗组间无显著差异。有趣的是，NO3-给药似乎加重了肾损伤。刷状缘丢失、肾小管坏死和红细胞外渗的组织学评分显示治疗组间无显著差异。结果表明，与NO2-在肝脏和心脏I/R损伤中的保护作用相反，NO2-在肾脏I/R损伤中不提供保护，并且表明NO2-在肾脏中的独特代谢。
Reactive oxygen and nitrogen species play a key role in the pathophysiology of renal ischemia-reperfusion (I/R) injury. Recent studies have shown that nitrite (NO2-) serves as an endogenous source of nitric oxide (NO), particularly in the presence of hypoxia and acidosis. Nanomolar concentrations of NO2- reduce injury following I/R in the liver and heart in vivo. The purpose of this study was to evaluate the role of NO2- in renal I/R injury. Male Sprague-Dawley rats underwent a unilateral nephrectomy followed by 45 min of ischemia of the contralateral kidney or sham surgery under isoflurane anesthesia. Animals received normal saline, sodium NO2-, or sodium nitrate (NO3-; 1.2 nmol/ g body wt ip) at 22.5 min after induction of ischemia or 15 min before ischemia. A separate set of animals received saline, NO2-, or NO3- (0.12, 1.2, or 12 nmol/ g body wt iv) 45 min before ischemia. Serum creatinine and blood urea nitrogen were increased following I/R injury but were not significantly different among treatment groups at 24 and 48 h after acute renal injury. Interestingly, NO3- administration appeared to worsen renal injury. Histological scoring for loss of brush border, tubular necrosis, and red blood cell extravasation showed no significant differences among the treatment groups. The results indicate that, contrary to the protective effects of NO2- in I/R injury of the liver and heart, NO2- does not provide protection in renal I/R injury and suggest a unique metabolism of NO2- in the kidney.