Efrati Shai, Berman Sylvia, Siman-Tov Yariv, Lotan Raffie, Averbukh Zhan, Weissgarten Joshua, Golik Ahuva
Nephrology Division, Research & Development Unit, Department of Internal Medicine A, Assaf Harofeh Medical Center, Zerifin 70300, and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Nephrol Dial Transplant. 2007 Jul;22(7):1873-81. doi: 10.1093/ndt/gfm113. Epub 2007 Mar 29.
Renal failure is a threatening side-effect of NSAID administration, consequent to NSAID-mediated abrogation of prostaglandin synthesis and resultant renal ischaemia. N-acetylcysteine (NAC) has renoprotective properties. We examined effects of NAC in a rat model of NSAID-induced renal failure.
Renal failure was generated in 80 rats by 6-day water deprivation and 3-day 15 mg/kg/day diclofenac injection. The rats were concomitantly treated, or not, by NAC, 40 mg/kg/day. Renal function was evaluated by cystatin C, creatinine and urea. Intrarenal blood flow was measured by laser Doppler. The kidneys were subjected to pathological examination or evaluation of intrarenal NO, H2O2 and PGE2.
NAC significantly attenuated deterioration of renal function in diclofenac-treated rats: cystatin C dropped from 2.8+/-0.35 to 2.2+/-0.67 mg/l, P=0.016; creatinine from 1.2+/-0.97 to 0.96+/-0.19 mg/dl, P=0.02; urea from 208.4+/-57.9 to 157.6+/-33.7 mg/dl, P=0.028. Diclofenac-inflicted hystopathological damage was significantly reduced following NAC treatment. Intrarenal medullar blood flow dropped by 51+/-12.4% in diclofenac-treated rats, but only by 14+/-3.39% in those receiving NAC after diclofenac injection (P<0.001). H2O2 was elevated in renal tissues of diclofenac-receiving rats, while decreased in NAC-treated animals. PGE2 release by diclofenac-treated rats dropped significantly, but was restored after NAC administration both in renal cortices (144.7+/-10.4 vs 19.7+/-1.5 pmol/ml, P<0.001) and medullae (148.5+/-7.3 vs 66.6+/-7.3 pmol/ml, P<0.001).
In this model of renal failure induced by NSAID administration combined with water deprivation, NAC treatment successfully attenuated the deterioration of renal function by inducing renal vasodilatation, decreasing oxidative stress via inhibition of intrarenal ROS content and restoration of intrarenal PGE2 release back to the basal levels.
肾衰竭是使用非甾体抗炎药（NSAID）的一种严重副作用，是由NSAID介导的前列腺素合成受阻及由此导致的肾缺血引起的。N-乙酰半胱氨酸（NAC）具有肾脏保护特性。我们在NSAID诱导的肾衰竭大鼠模型中研究了NAC的作用。
80只大鼠通过6天禁水和3天每天注射15mg/kg双氯芬酸诱导肾衰竭。这些大鼠同时接受或不接受每天40mg/kg的NAC治疗。通过胱抑素C、肌酐和尿素评估肾功能。用激光多普勒测量肾内血流。对肾脏进行病理检查或评估肾内一氧化氮（NO）、过氧化氢（H2O2）和前列腺素E2（PGE2）。
NAC显著减轻了双氯芬酸治疗大鼠的肾功能恶化：胱抑素C从2.8±0.35降至2.2±0.67mg/l，P = 0.016；肌酐从1.2±0.97降至0.96±0.19mg/dl，P = 0.02；尿素从208.4±57.9降至157.6±33.7mg/dl，P = 0.028。NAC治疗后，双氯芬酸造成的组织病理学损伤显著减轻。双氯芬酸治疗的大鼠肾内髓质血流下降了51±12.4%，但双氯芬酸注射后接受NAC治疗的大鼠仅下降了14±3.39%（P < 0.001）。接受双氯芬酸的大鼠肾组织中H2O2升高，而NAC治疗的动物中H2O2降低。双氯芬酸治疗的大鼠PGE2释放显著下降，但NAC给药后在肾皮质（144.7±10.4对19.7±1.5pmol/ml，P < 0.001）和髓质（148.5±7.3对66.6±7.3pmol/ml，P < 0.001）中均恢复。
在这种由NSAID给药联合禁水诱导的肾衰竭模型中，NAC治疗通过诱导肾血管舒张、抑制肾内活性氧（ROS）含量降低氧化应激以及将肾内PGE2释放恢复到基础水平，成功减轻了肾功能恶化。
