Kaur H, Padi S S V, Chopra K
Pharmacology division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Methods Find Exp Clin Pharmacol. 2003 Dec;25(10):803-9. doi: 10.1358/mf.2003.25.10.793329.
Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antiischemic agent trimetazidine in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping the unilateral renal artery for 45 min followed by 24 h of reperfusion. Trimetazidine (2.5 mg/kg i.p.) was administered 24 and 12 h prior to renal artery occlusion and the same dose was given intravenously 1 h before inducing ischemia. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance compared with sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. Trimetazidine markedly reduced elevated levels of TBARS and significantly attenuated renal dysfunction and morphological changes in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect and the therapeutic potential of trimetazidine, an anti-ischemic agent, in attenuating renal ischemia-reperfusion injury.
肾缺血再灌注损伤是急性肾衰竭最常见的致病因素，也是同种异体肾移植受者和血管重建手术中肾功能障碍的主要原因。许多研究表明，活性氧在缺血性急性肾衰竭中起重要作用。本研究的目的是探讨合成抗缺血药物曲美他嗪在大鼠肾缺血再灌注损伤模型中的作用。通过夹闭单侧肾动脉45分钟，然后再灌注24小时诱导肾缺血再灌注。在肾动脉闭塞前24小时和12小时腹腔注射曲美他嗪（2.5mg/kg），并在诱导缺血前1小时静脉注射相同剂量。以肾匀浆中硫代巴比妥酸反应物质（TBARS）测定组织脂质过氧化。通过估算血清肌酐、血尿素氮（BUN）、肌酐和尿素清除率来评估肾功能。通过对苏木精-伊红染色的肾脏切片进行组织病理学检查来评估肾脏形态学改变。与假手术大鼠相比，缺血再灌注导致TBARS水平升高，并使肾功能恶化，表现为血清肌酐、BUN升高，肌酐和尿素清除率降低。大鼠缺血肾脏表现出严重的透明管型、上皮肿胀、蛋白质碎片、肾小管坏死、髓质充血和出血。曲美他嗪显著降低了肾缺血再灌注大鼠升高的TBARS水平，并显著减轻了肾功能障碍和形态学变化。这些结果清楚地证明了抗缺血药物曲美他嗪在减轻肾缺血再灌注损伤方面的体内抗氧化作用和治疗潜力。
