Nrf2/ARE pathway mediates the reducing effect of Dexmedeto-midine on ischemia/reperfusion injury in skeletal muscle

doi:10.13459/j.cnki.cjap.2016.03.016

Abstract

Abstract: Objective:To explore the role of Nrf2/ARE pathway in skeletal muscle ischemia/reperfusion(I/R) injury preconditioning by dexmedetomidine(DEX). Methods:Twenty-eight SD rats were randomly divided into sham-operated(Sham group)、I/R group、I/R+ DEX(DEX group) and I/R+DEX +Atipamezole (Atip group). In the Atip group, Atip(250 μg/kg) and DEX(25 μg/kg) were injected together after anesthesia; In the Sham and I/R groups, the homologous saline was also injected at the same time; In the DEX group, the homologous DEX and saline were coinjected. After 30 minutes, the hind limb ischemia was induced by clamping the common femoral artery and ligaturing collateral circulation. After 3 h of ischemia, the clamp and tourniquet were removed and the rats underwent 2 h of reperfusion. We measured plasma concentrations of lactate dehydrogenase (LDH) and creatine kinase(CK). The gastrocnemius muscle was harvested and immediately stored at -80℃ for the assessment of malondialdehyde(MDA)、superoxide dismutase(SOD) and Nrf2/HO-1 protein detected by Western blot. The other section muscle was stored in triformol for immunohistochemical and HE staining. The wet/dry was also immediately detecting. Results:The levels of wet/dry、MDA、LDH、CK、Nrf2 and HO-1 were higher(P<0.05) while the level of SOD was lower(P<0.05) in the I/R group than those in sham group. The levels of wet/dry、MDA、LDH、CK were significantly lower(P<0.05) yet the levels of SOD and Nrf2/HO-1 were significantly higher(P<0.05) in DEX group than those in I/R group. However, Atip reversed the effect of DEX in Atip group, each of indicators had significant changes compared with those in the DEX group(P<0.05). Conclusion:Nrf2 protein was expressed in skeletal muscle of rat and DEX could promote its level in nucleus by α-adrenergic receptor. The down-stream products of Nrf2 have the effect of antioxidant.

Key words: ischemia/reperfusion injury, oxidative stress, NF-E2-related factor-2, dexmedetomidine, rat

YUAN Pei-gen, XUE Bin-bin, LIN Bi, ZHAO Xi-yue, ZHOU Sen, HU Yi, BAO Cai-ying, LIN Li-na. Nrf2/ARE pathway mediates the reducing effect of Dexmedeto-midine on ischemia/reperfusion injury in skeletal muscle[J]. CJAP, 2016, 32(3): 250-254.

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