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This study investigated the protective effect of Curcumin on renal ischemia-reperfusion injury (RIRI) as well as the mechanisms underlying the role of Curcumin. Selectivity of Curcumin in kidney in different doses and routes of administration was measured. In addition, the serum levels of β2-MG, UAER, BUN and creatinine were compared among the Sham, the RIRI model and the Curcumin + RIRI model groups. The expression of miR-146a iNOS, eNOS and nNOS, PKG, and caspase-3 among various groups was measured using real-time PCR and Western-blot analysis, while the levels of NO and cGMP in the samples were measured by ELISA. Finally, the effect of Curcumin on the transcriptional efficiencies of miR-146a, nNOS, eNOS and iNOS was studied using luciferase assay. The presence of mesoscale nanoparticles (MNPs) in the kidneys was safe. In addition, the accumulation of MNPs was in a dose-dependent manner and peaked at a dose of 25 mg/kg. The administration of Curcumin reduced the levels of serum β2-MG, UAER, BUN, creatinine as well as the score of renal tubule damage, therefore alleviating the symptoms induced by RIRI. Furthermore, the RIRI model group showed serious congestion and edema in the renal cortex and medulla, whereas the Curcumin + RIRI model group exhibited less renal tissue damage compared with that in the RIRI model group. Moreover, Curcumin enhanced miR-146a expression, while reducing the expression of nNOS, iNOS, cGPM, caspase-3 and PKG as well as the synthesis of NO. Curcumin may exert its effect by reducing the transcriptional efficiency of iNOS promoter, while increasing the transcriptional efficiency of miR-146a promoter. Furthermore, nNOS expression was negatively regulated by miR-146a. The protective effect of Curcumin against RIRI may be mediated by its regulation of cell apoptosis through the miR-146a/nNOS/NO/cGMP/PKG signaling pathway.
SHORT-AND LONG-TERM SYNERGISTIC RENOPROTECTION INDUCED BY ERYTHROPOIETIN DERIVED PEPTIDE AND CASPASE-3 SIRNA AGAINST RENAL ISCHEMIA/REPERFUSION INJURY IN MICE
