ArticleAnnals of translational medicine2022
The activation of SIRT3 by dexmedetomidine mitigates limb ischemia-reperfusion-induced lung injury.
Article in Annals of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Esketamine Reduces Lung Injury Caused by Limb Ischemia-Reperfusion by Regulating Oxidative Stress via the TLR4/NF-κB/NLRP3 PathwayEndocrine, metabolic & immune disorders drug targets · 2026Article
- The effect of Dexmedetomidine on remote organ injury in the lung in rats with pancreatic ischemia reperfusion model.BMC anesthesiology · 2025Article
- Identification of Hub Genes for Dexmedetomidine Alleviation of Limb Ischemia-Reperfusion-Induced Lung Injury in Rats by Transcriptomic.Journal of inflammation research · 2025Article
- A clinically-relevant mouse model that displays hemorrhage exacerbates tourniquet-induced acute kidney injury.Frontiers in physiology · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: The lung is one of the most sensitive organs, and is vulnerable to injury caused by limb ischemia-reperfusion (LIR). Dexmedetomidine, an anesthetic adjunct, has been shown to have therapeutic effects on lung injury secondary to LIR. This study aimed to investigate the role of dexmedetomidine in ameliorating LIR-induced lung injury in a mouse model of bilateral hind LIR. Methods: In this study, 75 mice were randomly divided into 5 groups to prepare the LIR model. After the model was established, arterial blood was extracted for blood gas analysis. The pathological changes of lung tissue, lung wet/dry weight ratio, arterial blood gas analysis, detection of myeloperoxidase (MPO) activity, the content of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in oxidative stress indexes, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and cytochrome c content were measured, and the relative protein expression levels of sirtuin-3 (SIRT3) and apoptosis factor Bcl-2 related X protein (Bax), B-cell Lymphoma 2 (Bcl-2), cleaved caspase 3, and nuclear factor erythroid 2-related factor 2 (Nrf2) and cytoplasmic heme oxygenase-1 (HO-1). Results: Pretreatment with dexmedetomidine dramatically ameliorated LIR-induced lung injury, the wet/dry weight ratio, the arterial blood gas parameters, and enhanced SIRT3 expression. Moreover, dexmedetomidine significantly inhibits ROS and MDA level and restores antioxidant enzyme activities (SOD, GSH-Px). Of note, dexmedetomidine suppressed LIR-induced lung tissue apoptosis by modulating apoptosis-associated protein such as Bax, Bcl-2, and cleaved caspase 3. Moreover, dexmedetomidine inhibited the LIR-induced decreases in MMP, ATP levels, and the release of cytochrome c of LIR to maintain mitochondrial function. Latest study has shown that activating Nrf2 could promote SIRT3 expression to alleviate IR injury. Intriguingly, dexmedetomidine could facilitate nuclear Nrf2 and cytoplasmic HO-1 expression. Conclusions: Our findings suggest that dexmedetomidine protects against LIR-induced lung injury by inhibiting the oxidative response, mitochondrial dysfunction and apoptosis. The mechanism appears to be at least partly mediated through the upregulation of SIRT3 expression.
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