Proteasome participates in the pathogenesis of ischemic acute renal failure in rats

摘要: Acute renal failure was induced by occlusion of the left artery and vein for 45 min followed reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow urinary osmolality were measured to test effectiveness drugs. in untreated acute rats markedly decreased at 24 h reperfusion. The administration PSI, N-benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal, a proteasome inhibitor, dose 1 mg/kg before abolished decreases rats. Calpeptin (1 mg/kg), calpain attenuated deterioration same extent 0.1 but no significant difference observed between calpeptin-treated groups. Histopathological examination kidney revealed severe lesions, tubular necrosis, proteinaceous casts tubuli medullary congestion, all which significantly suppressed PSI mg/kg) treatment. In contrast, calpeptin, dose, ineffective against development lesions. These results suggest that participates pathogenesis ischemic failure. Thus, may be potential target identification agents useful treatment diseases whose etiology is dependent on ischemia/reperfusion.