Kidney
ischemia-reperfusion (I/R) injury is a common cause of
acute kidney injury. We tested whether
dexmedetomidine (Dex), an alpha2
adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague-Dawley rats were divided into four groups: (1)
Sham-operated group; (2) I/R group (40 min
ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with
fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney
protein kinase B,
toll like receptor 4, light chain 3B,
p38 mitogen-activated protein kinase (
p38 MAPK),
sirtuin 1,
adenosine monophosphate kinase (AMPK), and
endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular
necrosis and inflammatory response. Neither pre- nor postconditioning with
fadolmidine protected kidneys. Dex decreased blood pressure more than
fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular,
integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas
aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning.