Ahmadiasl Nasser, Banaei Shokofeh, Alihemmati Alireza, Baradaran Behzad, Azimian Ehsan
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2014;4(1):49-54. doi: 10.5681/apb.2014.008. Epub 2013 Dec 23.
Renal ischemia reperfusion (IR) is an important cause of renal dysfunction. It contributes to the development of acute renal failure (ARF). The purpose of this study was to investigate the anti-inflammatory effect of erythropoietin (EPO) and melatonin (MEL), which are known anti-inflammatory and antioxidant agents, in IR-induced renal injury in rats.
Male Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10mg/kg, i.p) and EPO (5000U/kg, i.p) were administered prior to ischemia. After 24 h reperfusion, blood samples were collected for the determination of total antioxidant capacity (TAC), malondialdehyde (MDA) and serum creatinine levels. Also, renal samples were taken for Immunohistochemical evaluation of Bcl2 and TNF-α (tumor necrosis factor-α) expression.
Ischemia reperfusion increased creatinine, TAC, MDA levels and TNF-α expression, also, IR decreased Bcl2 expression. Treatment with EPO or MEL decreased creatinine, MDA levels, and increased TAC level. Also, MEL up-regulated Bcl2 expression and down-regulated TNF-α expression compared with EPO.
Treatment with EPO and MEL had a curative effect on renal IR injury. These results may indicate that MEL protects against inflammation and apoptosis better than EPO in renal IR injury.
肾缺血再灌注（IR）是肾功能障碍的重要原因，它会促使急性肾衰竭（ARF）的发展。本研究的目的是探讨促红细胞生成素（EPO）和褪黑素（MEL）这两种已知的抗炎和抗氧化剂对大鼠IR诱导的肾损伤的抗炎作用。
雄性Wistar白化大鼠单侧肾切除，肾蒂阻断45分钟，然后再灌注24小时。在缺血前给予MEL（10mg/kg，腹腔注射）和EPO（5000U/kg，腹腔注射）。再灌注24小时后，采集血样测定总抗氧化能力（TAC）、丙二醛（MDA）和血清肌酐水平。同时，取肾组织样本进行Bcl2和肿瘤坏死因子-α（TNF-α）表达的免疫组织化学评估。
缺血再灌注增加了肌酐、TAC、MDA水平和TNF-α表达，此外，IR降低了Bcl2表达。EPO或MEL治疗降低了肌酐、MDA水平，并提高了TAC水平。此外，与EPO相比，MEL上调了Bcl2表达，下调了TNF-α表达。
EPO和MEL治疗对肾IR损伤有治疗作用。这些结果可能表明，在肾IR损伤中，MEL比EPO能更好地预防炎症和细胞凋亡。
