The effect of Ephedra aqueous extract on lung injury of rats with Streptococcus pneumoniae pneumonia via regulating ROS/NLRP3/Caspase-1 pathway / 免疫学杂志

ABSTRACT

This study was performed to evaluate the role and mechanism of Ephedra aqueous extract in alleviating lung injury of rats with Streptococcus pneumoniae pneumonia via regulating reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/caspase-1 pathway.Male SD rats were randomly divided into control group,model group,Ephedra aqueous extract(100 mg/kg,200 mg/kg,400 mg/kg)groups,solvent control group(110 ml/kg DMSO),model+solvent group,high-dose Ephedra aqueous extract+solvent group,and high-dose Ephedra aqueous extract+trimethylamine N-oxide(TMAO,110 mg/kg)group.Pneumonia model was established by instilling Streptococcus pneumoniae solution into the trachea.After 24 hours of modeling,each group was given medication by gavage for 10 consecutive days.24 hours after the last gastric lavage,pathological changes in lung tissue and the contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α)in serum and bronchoalveolar lavage fluid(BALF)were detected;and the contents of malondialdehyde(MDA),superoxide dismutase(SOD),the activity of ROS and the expression levels of NLRP3,Caspase-1,GSDMD-N in lung tissue were detected.The model group rats demonstrated pathological changes in lung injury including thickening of alveolar septa and infiltration of inflammatory cells,as well as the contents of IL-1β,IL-6,TNF-α in BALF and serum,the content of MDA,the activity of ROS,the expression levels of NLRP3,Caspase-1 and GSDMD-N in lung tissue were higher than those of the control group,while the SOD content in lung tissue was lower than that of the control group(P<0.05).The lung injury of the low,medium,and high dose Ephedra aqueous extract groups were reduced,and the contents of IL-1β,IL-6,TNF-α in BALF and serum,the content of MDA,the activity of ROS,the expression levels of NLRP3,Caspase-1 and GSDMD-N in lung tissue were lower than that of the model group,while the SOD content in lung tissue was higher than that of the model group(P<0.05).The lung injury of rats in the high-dose ephedra aqueous extract+TMAO group worsened,the contents of IL-1β,IL-6,TNF-α in BALF and serum,the content of MDA,the activity of ROS,the expression levels of NLRP3,Caspase-1 and GSDMD-N in lung tissue were higher than those of the high-dose Ephedra aqueous extract+solvent group,while the SOD content in lung tissue was lower than that of the high-dose Ephedra aqueous extract+solvent group(P<0.05).In conclusion,Ephedra aqueous extract alleviates the lung injury of rats with Streptococcus pneumoniae pneumonia via inhibiting the inflammatory response,oxidative stress and pyroptosis mediated by ROS/NLRP3/Caspase-1 pathway.