DEXMEDETOMIDINE AMELIORATES ISCHEMIA/REPERFUSION-INDUCED ACUTE KIDNEY INJURY BY INHIBITING ENDOPLASMIC RETICULUM STRESS VIA THE NRF2 SIGNALING PATHWAY

Abstract

Objective: To investigate the effect of dexmedetomidine (Dex) on the expression of nuclear factor Erythroid 2-related factor 2 (Nrf2) and the activation of endoplasmic reticulum stress (ERS) in renal tissues during ischemia/reperfusion (I/R). Methods: C57BL/6 mice were selected and divided into Sham group, I/R group, Dex group and (Dex+I/R) group. Serum urea nitrogen (BUN) and creatinine (Cr) were detected, and the expressions of Nrf2, ER chaperone BiP (GRP78) and C/EBP homologous protein (CHOP) were detected by qPCR. Results: Compared with the Sham group, the serum levels of BUN and Cr were significantly elevated in I/R group, meanwhile, the expressions of Nrf2, GRP78 and CHOP in renal tissues were also significantly increased (P<0.05). Dex pretreatment significantly lowered serum levels of BUN and Cr, as well as inhibited intracellular expressions of GRP78 and CHOP, while obviously increased intracellular Nrf2 expression in renal tissues of I/R-treated mice (P<0.05). Conclusions: Dex has a protective effect on renal I/R injury, its mechanism may be related to the activation of Nrf2 expression and further inhibit the activation of ERS-related apoptotic pathways.