Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Chen,Yaping; Bian,Wenyu; Xu,Bo

doi:10.3892/mmr.2020.10942

Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Authors:
- Yaping Chen
- Wenyu Bian
- Bo Xu
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Affiliations: Department of Anesthesiology, Jinshan Hospital, Fudan University, Shanghai 200000, P.R. China, Department of Anesthesiology, Renji Hospital, Jiaotong University School of Medicine, Shanghai 200127, P.R. China, Department of Anesthesiology and SICU, Xinhua Hospital, Jiaotong University School of Medicine, Shanghai 200092, P.R. China
Published online on: January 14, 2020 https://doi.org/10.3892/mmr.2020.10942
Pages: 1233-1241
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the antioxidant mechanisms of dexmedetomidine against lung injury during intestinal ischemia reperfusion (IIR) in rats. The model of IIR‑induced acute lung injury was established by occluding the superior mesenteric artery (SMA) for 1 h and reperfusing for 2 h using Sprague‑Dawley rats. Pathological examination was used to assess the extent of the lung injury. Oxidative stress was evaluated by measuring malondialdehyde, myeloperoxidase and superoxide dismutase in the lung and plasma. The proinflammatory cytokines tumor necrosis factor‑α and interleukin‑6 were determined via an enzyme‑linked immunosorbent assay. The mRNA and protein expression of nuclear factor‑erythroid 2 related factor 2 (Nrf2) and heme oxygenase 1 (HO‑1) were determined using a reverse transcription‑quantitative polymerase chain reaction and western blotting. Pretreatment with dexmedetomidine significantly inhibited the oxidative stress response and proinflammatory factor release caused by IIR compared with the normal saline group (MDA and SOD in lung and plasma, P<0.05; MPO, IL‑1β and TNF‑α in lung and plasma, P<0.05). Dexmedetomidine improved pulmonary pathological changes in IIR rats compared with the normal saline group. Investigations into the molecular mechanism revealed that dexmedetomidine increased the expression levels of Nrf2 and HO‑1 via activating α2 adrenergic receptors compared with the normal saline group. The antagonism of α2 adrenergic receptors may reverse the protective effect of dexmedetomidine on lung injury during IIR, including decreasing the expression levels of Nrf2 and HO‑1, elevating the oxidative stress response and increasing the proinflammatory factor release. In conclusion, pretreatment with dexmedetomidine demonstrated protective effects against lung injury during IIR via α2 adrenergic receptors. The Nrf2/HO‑1 signaling pathway may serve a function in the protective effect of dexmedetomidine.

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