Abstract:【Objective】 To observe the therapeutic effect of Sirt1 agonist SRT1720 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. 【Methods】 Adult male C57bl/6 mice were randomly divided into control group, SRT1720 group, ALI group and ALI+SRT1720 group (8 mice in each group). Mice were injected intraperitoneally with LPS (10 mg/kg) to induce ALI model. Mice in the SRT1720 group and in the ALI+SRT1720 group were intraperitoneally injected with SRT1720 (100 mg/kg) 1 hour earlier before lPS injection. Then All mice were sacrificed 12 hours after LPS injection. H&E staining was used to observe pathological changes of lung tissue. The wet/dry ratio of lung tissue was measured. Inflammatory cells in bronchoalveolar lavage fluid (BLAF) were counted, and myeloperoxidation (MPO) activity in lung tissue was detected. The gene and protein expression of inflammatory factors (TNF-α and IL-1β) in lung tissue of mice were detected by real-time PCR and ELISA, respectively.【Results】 Compared to mice in the control group, mice in the SRT1720 treatment alone group had no effect on the morphology and inflammation of lung tissue. Intraperitoneal injection of LPS can induce pathological damage in lung tissue of mice, increase lung wet/dry ratio, increase the number of total cells and neutrophils in BALF, increase MPO activity, and increase the expressions of TNF-α and IL-1β in lung tissue. The mice in the ALI+SRT1720 group showed that SRT1720 treatment significantly reduced the changes described above.【Conclusion】 Sirt1 agonist SRT1720 can attenuate LPS-induced ALI in mice, and its mechanism is related to inhibition of inflammatory response.
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