RESUMEN
To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p< 0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p< 0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.
Asunto(s)
Animales , Humanos , Masculino , Ratas , Apoptosis , Western Blotting , Etiquetado Corte-Fin in Situ , Isquemia , Proteínas Quinasas JNK Activadas por Mitógenos , Isquemia Miocárdica , Miocitos Cardíacos , Naloxona , Ratas Sprague-Dawley , Daño por Reperfusión , ReperfusiónRESUMEN
The aim of this study is to clarify whether edaravone postconditioning had protective effect against renal ischemia/reperfusion injury and to compare the protective effect between ischemic postconditioning and edaravone postconditioning. Rats were subjected to 45 min ischemia followed by 24 h reperfusion. The rats were randomly assigned to seven groups: a sham-operated control group, an ischemia/reperfusion group, an ischemic postconditioning group, a normal saline vehicle postconditioning group and an edaravone postconditioning (1, 3, and 6 mg x kg(-1)) group. Renal function was assessed by serum creatinine and BUN concentration, while histological damage of renal tissue was assessed with HE staining. MDA content and SOD activity of renal tissue were determined. TUNEL staining was performed to analyze the apoptosis of the tubular epithelial cells, the protein level of Bcl-2 and Bax in renal tissue was examined by Western blotting. Compared to the ischemia/reperfusion group, edaravone postconditioning significantly decreased serum creatinine and BUN concentration, and ameliorated histological damage of renal tissue. MDA was less after 24 h reperfusion in the edaravone postconditioning group than that in the ischemia/reperfusion group, consistent with an increase in SOD activity. In addition, edaravone postconditioning decreased TUNEL-positive cells and Bax expression, and increased Bcl-2 expression. Results detected in the edaravone postconditioning group showed no significant difference from the ischemic postconditioning group. Edaravone administered during the last 3 min of ischemia, prior to reperfusion induces a pharmacological postconditioning in vivo against renal ischemia/reperfusion injury in rats. This protection is similar to that observed with ischemic postconditioning.