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Am J Physiol Renal Physiol ; 292(3): F1082-93, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17341718

RESUMO

Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Trimetazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241-2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495-504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1alpha) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage.


Assuntos
Traumatismo por Reperfusão/prevenção & controle , Trimetazidina/uso terapêutico , Isquemia Quente , Animais , Western Blotting , Creatinina/sangue , Expressão Gênica/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe II/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Córtex Renal/efeitos dos fármacos , Córtex Renal/metabolismo , Córtex Renal/patologia , Testes de Função Renal , Medula Renal/efeitos dos fármacos , Medula Renal/metabolismo , Medula Renal/patologia , Masculino , Nefrectomia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatmina/genética , Estatmina/metabolismo , Análise de Sobrevida , Sus scrofa , Fatores de Tempo , Resultado do Tratamento , Trimetazidina/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Vasodilatadores/uso terapêutico
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