Study on the protective mechanism of total glucosides of paeony to regulate cell pyroptosis against acute lung injury in septic rats
Objective To explore the effect and mechanism of total glucosides of paeony on acute lung injury in rats with sepsis.Methods Eighty male,SPF,SD rats were selected and divided into control group,model group,low-dose,medium-dose and high-dose total glucosides of paeony groups,dexamethasone group,caspase-1 inhibitor Z-YVAD group,paeonia lactiflora Total glycosides+Z-YVAD group,with 10 rats in each group.The acute lung injury model of sepsis rats was established by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide(LPS),and the rats in each group were continuously administered for 8 weeks.After administration,the wet/dry weight ratio(W/D)of lung tissue and the contents of inflammatory cytokines IL-1β,TNF-α and IL-6 in bronchoalveolar lavage fluid(BALF)of rats in each group were determined.The pathological changes of lung tissue were observed by red(HE)staining.The expression of CD31 in the vascular endothelium was detected by immunohistochemistry.The protein expressions of caspase-1,GSDMD-N,IL-1β and IL-18 were detected by Western blot.Results The lung tissue showed obvious pathological injury,and the W/D ratio,the contents of IL-1β,TNF-α and IL-6,and the expressions of caspase-1,GSDMD-N,IL-1β and IL-18 were significantly increased(P＜0.05).The low,medium and high dose groups of total glucosides of paeony can significantly improve the pathological damage of rat lung tissue and reduce the W/D ratio,IL-1β,TNF-αand IL-6 contents,caspase-1,GSDMD-N,IL-1β,IL-18 expression(P＜0.05);the above detection indexes could be further decreased after intraperitoneal injection of Z-YVAD in rats(P＜0.05).Conclusion Total glucosides of paeony has a protective effect on acute lung injury in septic rats,and the mechanism is related to the inhibition of caspase-1-mediated pyroptosis.
total glucosides of paeonysepsisacute lung injurypyroptosis
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