Departamento de Fisiología, Universidad Autónoma de Nuevo León, Facultad de Medicina, Monterrey, Nuevo León 64460, México.
Ren Fail. 2009;31(9):822-8. doi: 10.3109/08860220903151427.
Renal ischemia/reperfusion (I/R) occurs during shock and transplant procedures, greatly affecting outcome. A definitive treatment has not been found. One of the pathophysiological bases of renal I/R injury is the activation of the transcription factor nuclear factor-kappaB (NF-KappaB). We studied the effects of sulfasalazine (SFZ), a NF-kappaB inhibitor, over renal injury in a bilateral renal I/R model in rats. Ten male Wistar rats were subjected to bilateral renal I/R for 45 min followed by 24 h of reperfusion. Half of these received 100 mg/kg SFZ orally before the induction of I/R, while the others received only saline. Five rats served as sham-operated controls. At the end of the reperfusion period, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), P-selectin, tumor necrosis factor-alpha (TNF-alpha), intracellular adhesion molecule-1 (ICAM-1), and endothelin-1 (ET-1) concentrations were determined in serum, and renal samples were taken for histological evaluation. After renal I/R, AST, LDH, BUN, TNF-alpha, ICAM-1, and ET-1 serum levels were significantly increased, and tubules were severely damaged on histological analysis, compared to sham controls. SFZ treatment reduced the AST, LDH, BUN, TNF-alpha, and ET-1 elevations, as well as the tubular damage, induced by renal I/R. Serum ICAM-1 and P-selectin were unchanged. These results show that SFZ has a protective effect over renal IR injury. The modulation of adhesion molecules probably does not play a part in these effects, but TNF-alpha and ET-1 modulation could be partly responsible for the effects we observed.
肾缺血/再灌注（I/R）发生在休克和移植手术中，对结果有很大影响。目前尚未找到明确的治疗方法。肾 I/R 损伤的病理生理基础之一是转录因子核因子-κB（NF-κB）的激活。我们研究了 NF-κB 抑制剂柳氮磺胺吡啶（SFZ）对大鼠双侧肾 I/R 模型肾损伤的影响。10 只雄性 Wistar 大鼠行双侧肾 I/R 45 分钟，再灌注 24 小时。其中一半在诱导 I/R 前口服 100mg/kg SFZ，另一半仅给予生理盐水。5 只大鼠作为假手术对照。再灌注期末，测定血清天门冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、血尿素氮（BUN）、P-选择素、肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）和内皮素-1（ET-1）浓度，并取肾组织进行组织学评价。肾 I/R 后，AST、LDH、BUN、TNF-α、ICAM-1 和 ET-1 血清水平明显升高，组织学分析显示肾小管严重受损，与假手术对照组相比。SFZ 治疗可降低肾 I/R 引起的 AST、LDH、BUN、TNF-α和 ET-1 升高以及肾小管损伤。血清 ICAM-1 和 P-选择素无变化。这些结果表明 SFZ 对肾 I/R 损伤具有保护作用。黏附分子的调节可能不是这些作用的一部分，但 TNF-α和 ET-1 的调节可能部分解释了我们观察到的作用。
