| Salmonella typhimurium(S.typhimurium)is one of the most isolated and resistant serotypes of Salmonella,which usually lead to acute and chronic gastroenteritis and other local inflammation after infection.In severe cases,systemic infection also causes sepsis or even death.Therefore,new drug research is extremely urgent.Qi-xuan-tang(QXT)is a self-made traditional compound Chinese medicine with good antibacterial and anti-inflammatory activities.This research studied the effect of QXT on tissue damage of mice infected with S.typhimurium,and explored the mechanism of QXT.In this study,we established a mouse infection model by intraperitoneal injection of S.typhimurium.Set up three doses of QXT,125 mg/kg,250 mg/kg and 500 mg/kg.The drug was administered 3 days in advance and continued for 5 days.On the 4th day,except for the control group,each group of mice was intraperitoneally injected with 1×10~6 CFU of S.typhimurium,observed the clinical symptoms and dissection lesions of the infected mice,and detected the key proteins by Western Blot at 24 h after challenge,and analyzed the mechanism of QXT.The results are as follows:1.Study on the model of S.typhimurium infection in mice(1)The mortality rate of the mice in the 1×10~6 CFU group was close to half,and its weight of mice was significant decrease compare with control group(p<0.01).Therefore,1×10~6 CFU was determined as the concentration of challenge.(2)The peak time of death of mice after challenge was 12-24 h,and the expression of NLRP3 and caspase-1 p10 protein in the large intestine of the mice was significantly higher than that of the control group at 24 h,so 24 h was used as the sampling time of the follow-up experiment.2.Protective effect of QXT on mice infected with S.typhimurium.(1)The high concentration of 500 mg/kg of QXT can significantly reduce the mortality of S.typhimurium infection(p<0.05).(2)Different concentrations of QXT can alleviate the detachment of intestinal epithelial cells and inflammatory cell infiltration of lung in mice,and the high dose of 500 mg/kg group has the best effect.(3)Different concentrations of QXT can significantly inhibit the serum levels of interleukin(IL)-1?and interleukin(IL)-18 induced by S.typhimurium(p<0.01).3.Study on the mechanism of QXT.Compared with model group,different concentrations of QXT can significantly inhibit the expression of the essential protein GSDMD p30(p<0.01),which significantly inhibits the expression of inflammatory corpuscle NLRP3(p<0.01),as well as the expression levels of caspase-1 p10 and caspase-11 p20,which were the key proteins of canonical and non-canonical signaling pathway(p<0.01).In summary,QXT has protective effects on S.typhimurium-infected mice,which can significantly reduce the mortality of mice,improve the lesions of the large intestine and lungs,and reduce the level of inflammation.S.typhimurium infection is closely related to pyroptosis.QXT may inhibit the expression of the essential protein GSDMD p30 by inhibiting the expression of the key proteins caspase-1 p10 and caspase-11 p20 in the canonical and the non-canonical signaling pathway,thereby inhibiting the cell death and creating a protective effect on the body.These results will help to further study the compound Chinese medicine"Qi-xuan-tang"and prevent or treat diseases caused by S.typhimurium. |
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