Dexmedetomidine alleviates renal ischemia reperfusion injury via suppressing SLC2A1-mediated glycolysis.

Renal ischemia reperfusion injury (IRI) represents a significant factor in perioperative acute kidney injury (AKI), which in turn predisposes to acute renal failure. Dexmedetomidine (Dex) is an anesthetic drug with sedative and analgesic effects, and clinical evidence supports its renoprotective properties. However, the exact molecular mechanism of Dex's renoprotection remains unclear. Our research specifically focuses on the role of Dex in glycolysis mediated by solute carrier family 2 member 1 (SLC2A1). Here, the renal ischemia/reperfusion (I/R) mouse model and HK-2 oxygen-glucose deprivation/reoxygenation (OGD/R) cell model were established. Pharmacologically, the results showed that Dex ameliorated the injury induced by I/R and OGD/R. Mechanistically, renal IRI elevated SLC2A1 expression, whereas Dex decreased it. STF-31, an inhibitor of SLC2A1, attenuated renal IRI and inhibited glycolysis. Dex inhibited renal IRI in the presence of SLC2A1 but not in the absence. In vitro experiments similarly found this phenomenon. Additionally, Dex promoted SLC2A1 internalization followed by autophagic-lysosomal degradation, as evidenced by immunofluorescence staining and Western blot. In conclusion, Dex has been demonstrated to attenuate renal IRI by inhibiting SLC2A1-mediated glycolysis, which was regulated by SLC2A1 expression, internalization, and lysosomal degradation. The present study presents a novel mechanism by which Dex attenuates renal IRI from a metabolic perspective.