Silent information regulator type-1 mediates amelioration of inflammatory response and oxidative stress in lipopolysaccharide-induced acute respiratory distress syndrome

Yuan Zhan, Chunjian Yang, Qunhui Zhang, Li Yao
Journal of Biochemistry 2021 January 22
Silent information regulator type-1 (SIRT1) is crucial during the development of acute respiratory distress syndrome (ARDS). We aimed to explore whether SIRT1 activation could protect against ARDS. SIRT1 was activated by its agonist SRT1720. ARDS was induced by intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS). Lung injuries were determined by the lung wet/dry ratio, inflammatory cells in the broncho-alveolar lavage fluid (BALF) and histological analysis. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay. The accumulation of neutrophils was detected by myeloperoxidase activity. Oxidative stress was evaluated by malondialdehyde, reduced glutathione, superoxide dismutaseand catalase activities. The protein expression levels were detected using Western blot. SIRT1 activation, either by SRT1720 administration or recombinant SIRT1 expression eliminated high dose LPS-induced mortality in mice, attenuated lung injury, influenced cytokine release in BALF, and decreased oxidative stress in the lung tissues of ARDS mice. Mechanically, SRT1720 administration inhibited p65 phosphorylation in the lung tissues of ARDS mice. SIRT1 ameliorates inflammatory response and oxidative stress in LPS-induced ARDS.

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