RESUMO
The aim of the present study was to investigate the protective effect of ozone oxidative preconditioning (OOP) on renal oxidative stress injury in a rat model of kidney transplantation. Thirty-six male Sprague Dawley (SD) rats were randomly divided into three groups: A sham (S) group, a kidney transplantation (KT) group and an OOP and kidney transplantation (OOP+KT) group. In the S group, the rats' abdomens were opened and closed without transplantation. In the KT group, the rats received a left kidney from donor SD rats. In the OOP+KT group, donor SD rats received 15 OOP treatments by transrectal insufflations (1 mg/kg), once a day, at an ozone concentration of 50 µg/ml, before the kidney transplantation. Twenty-four hours after transplantation, the parameters of renal function of the recipients were measured. The morphology and pathological effects of renal allograft were examined using hematoxylin and eosin staining, periodic acid-Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry. Markers of oxidative stress were also detected using the thiobarbituric acid method, and expression levels of Nrf-2 and HO-1 were determined by western blot analysis. Blood urea nitrogen and creatinine levels were significantly decreased in the OOP+KT group compared with the KT group, and the morphology and pathological changes of renal allograft were also less severe. Meanwhile, the renal allograft cell apoptosis index was significantly higher in the KT group compared to the OOP+KT group (P<0.05). Levels of superoxide dismutase, glutathione and catalase in the renal allografts were significantly higher in the OOP+KT group compared to those in the KT group (P<0.05), while malondialdehyde levels were significantly lower in the OOP+KT group compared to those in the KT group (P<0.05). Western blot analysis indicated that the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) were significantly higher in the OOP+KT compared to the KT group (P<0.05). In conclusion, the mechanism by which OOP alleviates oxidative stress injury in renal transplantation may be related to the activation of the signaling pathways of Nrf-2/HO-1 and inhibition of renal tubular epithelial cell apoptosis.
RESUMO
PURPOSE: To investigate the effect of metformin on renal tubular epithelial cell apoptosis and inflammation after kidney ischemia/ reperfusion in rats. METHODS: Eighteen SD rats were randomly divided into three groups: Sham (S), Ischemia/reperfusion (I/R), and Metformin (E). Before establishing the I/R model, group E was administered metformin for three days, while groups S and I/R were administered equal volumes of saline. After three days, a right nephrectomy was performed on all groups, after which the left kidneys of groups E and I/R rats were subjected to 45 min renal ischemia. Renal function, histology, and cell apoptosis were assessed. AMPK, pAMPK, COX-2, and Caspase 3 were also detected. RESULTS: Compared to I/R group, Caspase 3 and COX-2 levels were decreased in group E. COX-2, Caspase3 and pAMPK levels were higher in groups E and I/R than in group S. The pAMPK level of group E was higher than that of I/R group, while COX-2 and caspase 3 were lower in group E than they were in the other groups. There was no significant difference between E and I/R groups in AMPK levels. CONCLUSION: Metformin preconditioning attenuated the inflammation caused by ischemia/reperfusion and inhibited the apoptosis of renal tubular epithelial cells.
Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Precondicionamento Isquêmico/métodos , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Metformina/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Proteínas Quinases Ativadas por AMP/análise , Animais , Nitrogênio da Ureia Sanguínea , Western Blotting , Caspase 3/análise , Creatinina/sangue , Ciclo-Oxigenase 2/análise , Imuno-Histoquímica , Rim/patologia , Masculino , Distribuição Aleatória , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
PURPOSE:To investigate the effect of metformin on renal tubular epithelial cell apoptosis and inflammation after kidney ischemia/ reperfusion in rats.METHODS:Eighteen SD rats were randomly divided into three groups: Sham (S), Ischemia/reperfusion (I/R), and Metformin (E). Before establishing the I/R model, group E was administered metformin for three days, while groups S and I/R were administered equal volumes of saline. After three days, a right nephrectomy was performed on all groups, after which the left kidneys of groups E and I/R rats were subjected to 45 min renal ischemia. Renal function, histology, and cell apoptosis were assessed. AMPK, pAMPK, COX-2, and Caspase 3 were also detected.RESULTS:Compared to I/R group, Caspase 3 and COX-2 levels were decreased in group E. COX-2, Caspase3 and pAMPK levels were higher in groups E and I/R than in group S. The pAMPK level of group E was higher than that of I/R group, while COX-2 and caspase 3 were lower in group E than they were in the other groups. There was no significant difference between E and I/R groups in AMPK levels.CONCLUSION:Metformin preconditioning attenuated the inflammation caused by ischemia/reperfusion and inhibited the apoptosis of renal tubular epithelial cells.