Ahmadiasl Nasser, Banaei Shokofeh, Alihemati Alireza, Baradaran Behzad, Azimian Ehsan
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Clin Exp Nephrol. 2014 Dec;18(6):855-64. doi: 10.1007/s10157-014-0937-6. Epub 2014 Feb 4.
Renal ischemia reperfusion (IR) is an important cause of renal dysfunction. It contributes to the development of acute renal failure. Oxidative damage from reactive oxygen species is considered to be the principal component involved in the pathophysiological tissue alterations observed during IR. The purpose of this study was to evaluate the effect of a combined treatment with erythropoietin (EPO) plus melatonin (MEL), which are known anti-inflammatory and antioxidant agents, in IR-induced renal injury in rats.
Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h of reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to ischemia. After 24 h of reperfusion, blood samples were collected for the determination of superoxide dismutase (SOD), glutathione peroxidase (GPx), plasma levels of total antioxidant capacity (TAC), and malondialdehyde (MDA) and serum urea level. Also, renal samples were taken for histological evaluation.
Ischemia reperfusion significantly increased urea, blood SOD, and GPx levels. Histological findings of the IR group indicated that there was increase in tubular and glomerular hyaline cast, thickening of Bowman capsule basement membrane, and renal impairment in the glomerular epithelium. Treatment with EPO and MEL significantly decreased blood SOD, GPx, and urea levels and increased TAC level. In the EPO + MEL group, while the histopathological changes were lower than those in EPO group, they were the same as MEL group.
EPO and MEL combination treatment exerted more nephroprotective effects than EPO treatment and nearly had protective effects similar to MEL treatment.
肾缺血再灌注(IR)是肾功能障碍的重要原因。它会导致急性肾衰竭的发生。活性氧引起的氧化损伤被认为是IR期间观察到的病理生理组织改变的主要组成部分。本研究的目的是评估促红细胞生成素(EPO)联合褪黑素(MEL)(已知的抗炎和抗氧化剂)治疗对大鼠IR诱导的肾损伤的影响。
将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,采集血样测定超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、总抗氧化能力(TAC)、丙二醛(MDA)血浆水平和血清尿素水平。此外,取肾组织样本进行组织学评估。
缺血再灌注显著提高了尿素、血SOD和GPx水平。IR组的组织学结果表明,肾小管和肾小球透明管型增加,鲍曼囊基底膜增厚,肾小球上皮出现肾损伤。EPO和MEL治疗显著降低了血SOD、GPx和尿素水平,并提高了TAC水平。在EPO+MEL组中,组织病理学变化低于EPO组,但与MEL组相同。
EPO和MEL联合治疗比EPO治疗具有更强的肾保护作用,且与MEL治疗的保护作用相近。