Resveratrol (Res) is a multi-functional
polyphenol compound that has protective functions in acute
kidney diseases. Here, we examined whether the
resveratrol could ameliorate post-contrast
acute kidney injury (PC-AKI) following
diabetic nephropathy (DN), and explored any underlying mechanism(s) in vivo and in vitro. Twenty-four rabbits with DN were randomly divided into four groups: control (Cont),
resveratrol (Res),
iohexol (PC-AKI), and
resveratrol plus
iohexol (Res+PC-AKI) groups. Functional magnetic resonance imaging, renal histology, blood and urinary
biomarkers, silent information regulator l (
SIRT1),
peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),
hypoxia-inducible transcription factor-1α (HIF-1α), and apoptosis-associated
protein expression were assessed ex vivo. For in vitro experiments, renal tubular epithelial (HK-2) cells subjected to high
glucose conditions were treated with
resveratrol, Ex527, an
SIRT1 inhibitor, or
2-methoxyestradiol (2-MeOE2), HIF-1α inhibitor, before treatment with
iohexol. With regard to the rabbit model of
acute renal injury in DN, compared to the PC-AKI group, the Res+PC-AKI group showed decreased levels of
cystatin C and urinary
neutrophil gelatinase-associated lipocalin, increased pure molecular diffusion (D) and the fraction of water flowing in capillaries (f), a decreased apparent relaxation rate (R2*), renal injury score and apoptosis rate, increased
protein expression levels of
SIRT1 and PGC-1α, and decreased levels of HIF-1α and apoptosis-associated
protein. In addition,
iohexol decreased HK-2 cell survival and increased the cell apoptosis rate; results were reversed after treating cells with
resveratrol.
Resveratrol reduced renal
hypoxia,
mitochondrial dysfunction and renal tubular cell apoptosis by activating SIRT1-PGC-1α-HIF-1α signaling pathways in PC-AKI with DN.