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  • Title: Sivelestat improves acute lung injury by inhibiting PI3K/AKT/mTOR signaling pathway.
    Author: Zhou Y, Wang H, Liu A, Pu Z, Ji Q, Xu J, Xu Y, Wang Y.
    Journal: PLoS One; 2024; 19(6):e0302721. PubMed ID: 38935660.
    Abstract:
    OBJECTIVE: To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL). METHODS: A rat model for ALI/acute respiratory distress syndrome (ALI/ARDS) was established. Pathological examination of lung tissue was conducted to assess lung injury. Blood gas in the arteries was measured using a blood analyzer. Changes in PaO2, PaO2/FiO2, and lung wet/dry (W/D) weight ratio were carefully compared. ELISA assay was conducted to estimate cell adhesion and inflammation response. Finally, real-time reverse transcription polymerase chain reaction and western blotting assay was used to determine the activation of PI3K/AKT/mTOR pathway. RESULTS: ARDS in vivo model was successfully constructed by LPS injection. Compared with the sham group, PaO2 and PaO2/FiO2 were significantly lower in the vehicle group, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8 andTNF-αwere significantly increased. After treatment with different doses of sivelestat sodium, we found PaO2, PaO2/FiO2 were prominently increased, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8, TNF-α levels were decreased in the dose-dependent manner. Meanwhile, compared with the vehicle group, the expression levels of Bax, PI3K, Akt and mTOR were significantly lower, and the expression of Bcl-2 was significantly higher after injection with sivelestat sodium. CONCLUSION: Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway.
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