Role and mechanism of ginsenoside Rg1 in ameliorating sepsis-induced acute lung injury based on PERK/eIF2α/ATF4/CHOP-induced alveolar epithelial cell apoptosis
The study investigates the therapeutic effects and mechanisms of ginsenoside Rg1(GRg1)on sepsis-induced acute lung injury(SALI).A murine model of SALI was created using cecal ligation and puncture(CLP)surgery,and mice were randomly as-signed to groups for GRg1 intervention.Survival and body weight changes were recorded,lung function was assessed with a non-invasive lung function test system,and lung tissue damage was evaluated through HE staining.The content and expression of inflammatory fac-tors were measured by ELISA and qRT-PCR.Apoptosis was examined using flow cytometry and TUNEL staining.The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3),B-cell lymphoma-2(Bcl-2),Bcl-2 as-sociated X protein(Bax),and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK),eukaryotic initiation factor 2α(eIF2α),activating transcription factor 4(ATF4),and C/EBP homologous protein(CHOP)were studied using Western blot and qRT-PCR.In addition,an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used,with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the ac-tion mechanism of GRg1.Results indicated that,when compared to the model group,GRg1 intervention significantly enhanced the sur-vival time of CLP mice,mitigated body weight loss,and improved impaired lung function indices.The GRg1-treated mice also dis-played reduced lung tissue pathological scores,a reduced lung tissue wet-to-dry weight ratio,and lower protein content in the bron-choalveolar lavage fluid.Serum levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α),as well as the mRNA expressions of these cytokines in lung tissues,were decreased.There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells,and down-regulated expressions of caspase-3,Bax,PERK,eIF2α,ATF4,and CHOP and up-regulated expression of Bcl-2 were observed.In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg1 were significantly inhibited with the co-application of tunicamycin.Altogether,GRg1 reduces apoptosis of alveolar epi-thelial cells,inhibits inflammation in the lungs,alleviates lung injury,and enhances lung function,possibly through the PERK/eIF2a/ATF4/CHOP pathway.
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