Sivelestat activates PPARγ/PGC1α/NRF2 signaling pathway to improve inflammatory response in mice with acute lung injury
Objective To investigate the effects of sivelestat on mitochondrial dysfunction and inflammatory response induced by acute lung injury in mice and the possible mechanism.Methods Thirty C57BL/6 mice were randomly divided into control group,acute lung injury group and sivelestat group,with 10 mice in each group.The pathological changes of lung tissues were observed by HE staining;the ROS level and mitochondrial membrane potential were observed by kit and fluorescence microscope;the levels of TNF-α,IL-1β and IL-6 in bronchoalveolar lavage fluid were detected by ELISA;the protein expression levels of mitochondrial and cytoplasmic Drp1,Mfn2,PPARγ,pgC1α and NRF2 were detected by Western blot.Results Sivelestat treatment improved the pathological damage of lung tissues in mice with acute lung injury,reduced the ROS level in lung tissues,increased the mitochondrial membrane potential in lung tissues,down-regulated the protein expression of mitochondrial Drp1 in lung tissues and up-regulated the protein expression of cytoplasmic Drp1 in lung tissues and Mfn2,PPARγ,pgC1α and NRF2 in cells,and reduced the levels of TNF-α,IL-1β and IL-6 in bronchoalveolar lavage fluid.Conclusion Sivelestat improves mitochondrial dysfunction,reduces inflammatory response and improves lung injury induced by acute lung injury,and the mechanism may be related to the activation of PPAR-γ/PGC1α/NRF2 signaling pathway.
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