Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Department of Infectious Diseases, University Duisburg-Essen, Essen, Germany.
Kidney Blood Press Res. 2017;42(6):1090-1103. doi: 10.1159/000485606. Epub 2017 Dec 5.
BACKGROUND/AIMS: The natural polyphenol resveratrol (RSV) has been shown to ameliorate ischemia/reperfusion (I/R)-induced damage. Therefore, a rat model of I/R-induced AKI equipped with intensive monitoring was utilized to examine direct renal protection by RSV in vivo.
AKI was induced by bilateral renal clamping (45 min) followed by reperfusion (3 h). Solvent-free RSV was continuously infused intravenously (0.056 and 0.28 mg/kg) in a total volume of 7 ml/kg/h starting from 30 min before renal clamping. At a mean arterial blood pressure below 70 mmHg for more than 5 min, bolus injections of 0.5 ml 0.9% NaCl solution were administered repetitively (max. 5 ml/kg/h).
No differences could be found between normoxic control groups with/without RSV. Bilateral renal clamping and subsequent reperfusion caused a progressive rise in creatinine, cystatin C, and CK, a decrease in cellular ATP content and diuresis. Infusion of RSV increased sirtuin 1 expression after ischemia/reperfusion and was associated with decreased blood pressure during ischemia and early reperfusion accompanied by an increased requirement of bolus injections as well as with increased expression of TNFα.
RSV did not exert protective effects on I/R-induced AKI in the present short-term in vivo rat model. The lack of protection is potentially connected to aggravation of blood pressure instability.
背景/目的:天然多酚白藜芦醇(RSV)已被证明可改善缺血/再灌注(I/R)引起的损伤。因此,利用配备强化监测的 I/R 诱导 AKI 大鼠模型,在体内检查 RSV 对肾脏的直接保护作用。
通过双侧肾脏夹闭(45 分钟)然后再灌注(3 小时)诱导 AKI。从肾脏夹闭前 30 分钟开始,以 7ml/kg/h 的总量持续静脉输注无溶剂 RSV(0.056 和 0.28mg/kg)。当平均动脉血压低于 70mmHg 超过 5 分钟时,重复给予 0.5ml 0.9%生理盐水的推注(最大剂量为 5ml/kg/h)。
在有/无 RSV 的正常氧对照组之间未发现差异。双侧肾脏夹闭和随后的再灌注导致肌酐、胱抑素 C 和 CK 逐渐升高,细胞内 ATP 含量和尿量减少。RSV 输注可增加缺血/再灌注后的 Sirtuin 1 表达,并与缺血期间和早期再灌注期间血压降低有关,同时需要更多的推注,以及 TNFα 的表达增加。
在本短期体内大鼠模型中,RSV 对 I/R 诱导的 AKI 没有保护作用。缺乏保护作用可能与血压不稳定的加重有关。