08 February 2020 : Animal Research
The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway
Ronghui Wang1ACDG*, Yongxiang Xie2AE, Jiwei Qiu3BD, Jueying Chen3CFDOI: 10.12659/MSM.919213
Med Sci Monit 2020; 26:e919213
Abstract
BACKGROUND: This study aimed to investigate the effects of dexmedetomidine in a rat model of sepsis-induced lung injury and the role of the adenosine monophosphate-activated protein kinase (AMPK) gene and silent information regulator 1 (SIRT1) gene signaling pathway.
MATERIAL AND METHODS: Sixty 28-week-old healthy male Sprague-Dawley rats were randomly divided into three groups, the sham group, the model group, and the dexmedetomidine-treated group. The rat model of sepsis-induced lung injury was developed by surgical cecal ligation and puncture. Lung tissues examined histologically in the three study groups. Cell apoptosis was measured using the TUNEL assay, and the expression of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10 were measured in rat lung tissue by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated proteins and AMPK/SIRT1 pathway-associated protein expression levels were detected using Western blot.
RESULTS: Dexmedetomidine significantly increased the survival rate and reduced the body temperature of rats in the model group with sepsis-induced lung injury, reduced lung injury, significantly reduced apoptosis in lung tissues, and reduced the expression levels of TNF-α, and IL-1β, and increased the levels of IL-10. Dexmedetomidine significantly reduced the expression of caspase-3 in the rat lung tissue (P<0.01), and significantly increased the expression of Bcl-2/Bax and the phosphorylation levels of AMPK, SIRT1, nuclear factor-κB (NF-κB), and forkhead box class O 3a (FOXO3a).
CONCLUSIONS: In a rat model of sepsis-induced lung injury, dexmedetomidine reduced lung damage by activating the AMPK/SIRT1 signaling pathway and reduced the expression of inflammatory cytokines and cell apoptosis.
Keywords: Lung Injury, Sepsis, AMP-Activated Protein Kinases, Body Temperature, Cytokines, Dexmedetomidine, Inflammation Mediators, Lung, Sirtuin 1
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