Aims: To evaluate the utility of
fasudil in a rat model of contrast-associated
acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI +
Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post
iopromide/
fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of
cystatin C (CysC) and interleukin-1β (IL-1β), and urinary
neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory
biomarkers, in addition to examining renal histology and expression levels of various
proteins (
Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]),
hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) that regulate renal
fibrosis and
hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1β, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1-13) in the CA-AKI +
Fasudil group (vs. CA-AKI) (all p < 0.05).
Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1
proteins induced by
iopromide, decreasing TGF-β1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05).
Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI,
fasudil appears to reduce renal
hypoxia,
fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-β1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during
fasudil therapy.