The Establishment Of A New Rat Model Of Urinary Tract Infection And The Study Of Traditional Chinese Medicine Prescriptions On ESBLs-producing Escherichia Coli-induced Complex Urinary Tract Infection In Rat

The First Part A rat model of urinary tract infection was established with bladder foreign body and ESBLs of E.coli injection without surgical manipulation.Objective:To explore the feasibility of establishing a rat model of urinary tract infection by using transurethral indwelling bladder foreign body with ESBLs Escherichia coli.Methods:30 female rats were randomly divided into blank control group,7 days and 14 days no foreign body groups,7 days and 14 days foreign body groups(n=6).The spiral polyethylene tube and ESBLs of E.coli was injected slowly into bladder through the urethra in the foreign body groups.No foreign body and blank groups were injected with ESBLs producing Escherichia coli and sterile saline.Flow cytology was performed to check blood leukocytes and neutrophil counts,Urine bacterial culture by blood agar plate,kidney HE staining.Results:The positive rate of urine bacteria in the 7d and14 d groups of foreign bodies was 100%;the positive rate of urine bacteria in the 7d group without foreign bodies was 33.3%,and the bacteria in the 14 d group without foreign bodies were free of bacteria;the pathology of HE in the7 d group of foreign bodies showed obvious inflammatory changes,foreign bodies A small amount of fibrous tissue was observed around the glomeruli in the 14 d group.There was a small amount of inflammatory cell infiltration,vasodilation,and congestion in the kidney of the 7d group without urine.No obvious inflammatory changes were observed in the 14 d group without foreign body.The percentage of neutrophils in the 14 d group was higher than that in the non-foreign group and the blank group(P<0.05).The number of white blood cells in the 7d group was higher than that in the 7d group and the blank group(P<0.05).Conclusion:The establishment of a highly successful and stable urinary tract infection rat model can be successfully achieved by transurethral injection of ESBLS with the bladder foreign body.The Second Part The effect of Chinese Herbs on Complex Urinary Tract Infection Induced by ESBLs-induced Escherichia Coli in RatsObjective: To explore the effect of traditional Chinese medicine prescription on complex urinary tract infection caused by ESBLs-producing Escherichia coli and its possible mechanism,and provide the experimental basis for clinical Chinese medicine treatment of ESBLs Escherichia coli complicated urinary tract infection.Methods: 66 female SD rats were randomly divided into blank control group and amoxicillin clavulanate potassium group,(n=5),model group,levofloxacin group,Bazhengsan group,levofloxacin + Fuzheng Qingre Tonglin group,Bazheng San(The first 7d)+ Fuzheng Qingre Tonglin group(the post7d)and Fuzheng Qingre Tonglin group(low and high dose)(n=8);The blank group was injected with sterile physiological saline,and the other groups were placed into the foreign body by the urethra and injected with the same amount of ESBLs Escherichia coli.After 2 weeks of treatment,the samples were sacrificed;and the number of peripheral white blood cell(WBC)and neutrophilic granulocyte percentage(NEUT%)were detected by flow cytometry;the peripheral blood urea nitrogen(BUN)and blood creatinine(CREA)was detected by the urease-glutamate dehydrogenase method and sarcosine oxidase method;the concentration of C-reactive protein(CRP),CD4+,CD8+ and urine SIg A,NAG molecules were detected by ELISA;Urine bacterial culture by blood agar plate,kidney HE staining.Results:The NEUT% and CRP: blank group,treatment groups(except levofloxacin group)were significantly lower than model group(P<0.05).The urine bacterial culture positive rate and counts:The positive rates of blank group,amoxicillin clavulanate potassium group,levofloxacin + Fuzheng Qingre Tonglin group and levofloxacin group were 0,0,40%,and 80%,respectively.The positive rates of the other groups were 100%.BUN: The blank group and treatment groups were lower than the model group.CREA: blank group and treatment groups were lower than the model group(except levofloxacin group).Urine SIg A: amoxicillin clavulanate potassium group,levofloxacin + Qingre Tonglin group,Bazhengsan group and Fuzheng Qingre Tonglin low dose group were higher than the model group,and the Bazhengsan + Fuzheng Qingre Tonglin group was significantly increased(P<0.05).Urine NAG: the blank group and treatment groups were lower than the model group(P<0.05).Blood CD4: the blank group and treatment groups were lower than the model group.Among those groups,the blank group,amoxicillin clavulanate potassium group,Bazhengsan + Fuzheng Qingre Tonglin group,Fuzheng Qingretong high dose group,levofloxacin + Fuzheng Qingre The Tonglin group were more obvious(P<0.05).The CD8: the blank group and treatment groups were higher than the model group,and the blank group,amoxicillin clavulanate potassium group,Bazhengsan + Fuzheng Qingre Tonglin group,Fuzheng Qingre Tonglin low-dose group,levofloxacin +Fuzheng Qingre Tonglin group were significantly higher than the model group.(P<0.05).Renal HE pathology: In the model group,a large number of inflammatory cells were seen in the kidney,a few fibrous tissues proliferated,and a large number of epithelial cells were necrotic,shedding,and cell tube formation.There was no significant improvement in the levofloxacin group compared with the model group.Levofloxacin + Fuzheng Qingre Tonglin group local proximal tubule dilatation,no obvious inflammation.Fuzheng Qingre Tonglin low-dose group showed more inflammatory cells in the kidney,and a few collecting tubes were necrotic,shedding,and tube formation.There were a few inflammatory cells in the local high-dose group of Bazheng San group,Bazhengsan + Fuzheng Qingre Tonglin group and Fuzheng Qingre Tonglin.The local proximal tubules were dilated and the epithelial cells were flat.There were no obvious abnormalities in the blank group and the amoxicillin clavulanate potassium group.Conclusion:1.Traditional Chinese medicine prescription can alleviate systemic and local inflammation of complicated urinary tract infection in rats.2.Traditional Chinese medicine prescription can regulate the immune function of rats with complex urinary tract infection and protect kidney function.3.Traditional Chinese medicine may reverse bacterial resistance and let the insensitive antibiotics re-effectively treat the resistant bacteria.