Key result
In a rat model of sepsis-induced lung injury, dexmedetomidine reduced lung damage and significantly reduced the expression of caspase-3 (P<0.01) via the AMPK/SIRT1 pathway.
Why the study?
This study aimed to investigate the effects of dexmedetomidine in a rat model of sepsis-induced lung injury and the role of the AMPK and SIRT1 signaling pathway.
Does dexmedetomidine reduce lung injury in a rat model of sepsis?
RCT (n=60)
randomly divided
Does dexmedetomidine reduce lung injury in a rat model of sepsis?
Dexmedetomidine reduces sepsis-induced lung injury in rats by activating the AMPK/SIRT1 signaling pathway.
Should not yet alter sepsis management; hypothesis-generating for AMPK/SIRT1-mediated lung protection in humans.
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-alpha (TNF-alpha), interleukin-1ß (IL-1ß), 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-alpha, and IL-1ß, 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-kappaB (NF-kappaB), 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.
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Wang et al. (2020) conducted an RCT in sepsis-induced lung injury (n=60). Dexmedetomidine vs. model group (sepsis without treatment) and sham group was evaluated on caspase-3 expression in rat lung tissue (p=<0.01). In a rat model of sepsis-induced lung injury, dexmedetomidine reduced lung damage and significantly reduced the expression of caspase-3 (P<0.01) via the AMPK/SIRT1 pathway.
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