Study On Therapy Effect Of EBSELEN Combined With Silver On Multi-drug-resistant Escherichia Coli-induced Cystitis In Mice

Objective To study the therapeutic effect of EBSELEN combined with silver ions on multidrug-resistant(MDR)Escherichia coli-induced cystitis in mice through targeting thioredoxin(Trx)and glutathione(GSH)systems.Methods(1)The MIC was calculated to determine the antibacterial effect of EBSELEN combined with Ag ions on MDR urinary pathogenic E.coli BC1;PI staining and transmission electron microscopy were used to detect the bactericidal effects of EBSELEN combined with Ag ions on MDR urinary pathogenic E.coli BC1.(2)The effects of EBSELEN combined with Ag ions on the activities of Trx and GSH systems,and redox state of BC1 were detected by ROS probe,DTNB experiment,and Western Blot assay.(3)Establish a bacterial cystitis mouse model by bladder perfusion bacterial method,intraperitoneal injection of EBSELEN and Ag ions,and the urine analyzer was used to detect the bacterial load in mouse bladder,white blood cell count,and red blood cell;TNFα and IFNγ in bladder epithelial cells was detected by immunohistochemistry.The mouse survival rate was calculated and the effects of the drug on liver and kidney function in mice were also measured.Results(1)EBSELEN combined with Ag ions can effectively kill BC1.(2)EBSELEN combined with Ag ions can inhibit the activity of BC1 Trx R,reduce the GSH amount and increase the active oxygen in bacteria.(3)EBSELEN combined with Ag ions can effectively reduce the amount of bladder bacteria,white blood cell and red blood cell and TNFα and IFNγ in cystitis mice,and have protective effects on cystitis mice without toxicity.Conclusion EBSELEN combined with Ag ions by inhibiting the activity of BC1 Trx R,reducing the GSH amount leading to an increase in intracellular active oxygen to kill BC1;reducing the bladder bacteria load in bacterial cystitis mice,improving mice bladder inflammation status.Therefore,EBSELEN combined with Ag ion showed therapeutic effect on BC1 induced cystitis mice by targeting Trx and GSH systems.