Effect of"Fuzheng Qingretonglin"decoction on complex urinary tract infection in rats by regulating NLRP3 inflammasome pathway

Obiective:To investigate whether"Fuzheng Qingretonglin"decoction can reduce urinary tract damage caused by complex urinary tract infection caused by drug resistant Escherichia coli by regulating Nod-like receptor pyrin domain3 inflammasome,and to explore the feasibility of this decoction combined with levofloxacin in the treatment of complex urinary tract infection caused by drug resistant bacteria.Methods:SD rats were divided into five groups:sham group,model group,levofloxacin group(Lev group),levofloxacin+Fuzheng Qingre Tonglin decoction group(FZ+lev group),and Fuzheng Qingre Tonglin decoction group(FZQRTL group).After the experiment,urine was taken for bacterial culture to determine the urinary tract infection of rats in each group;HE staining was used to observe the pathological changes of kidney and bladder tissues in rats;The expression of NLRP3 in kidney and bladder tissues was detected by immunohistochemistry;The expression of IL-1βand IL-18 in serum of rats was detected by ELISA;The expressions of NLRP3,ASC and Caspase-1 were detected by Western blotting.Results:The positive rate of urine bacteria culture in the sham group was 0%,the positive rate of urine bacteria culture in the model group was 100%;and the positive rate of urine bacteria culture in the FZ+lev group was 37.50%,which was statistically different from that in the model group(P<0.05).A large number of inflammatory cells were observed in the kidney and bladder tissues of the model group by HE staining,while the number of inflammatory cells in the kidney and bladder tissues of the Lev group and FZQRTL group was significantly reduced compared with that of the model group.The FZ+lev group in the number and structure of inflammatory cells in kidney and bladder were similar to the sham group.The NLRP3 immunohistochemistry of kidney and bladder tissue in FZ+lev groups and FZQRTL groups was significantly different from that in model group(P<0.001).The levels of IL-1βand IL-18 in serum of Lev group,FZQRTL group and FZ+lev group were significantly decreased by ELISA compared with model group(P<0.001).The levels of IL-1βand IL-18 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group,and the differences were statistically significant(P<0.05).The protein expressions of NLRP3,ASC and Caspase-1 in the Lev group,FZQRTL group and FZ+lev group were significantly lower than those in the model group(P<0.001).The protein expressions of NLRP3,ASC and Caspase-1 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group,and the differences were statistically significant(P<0.05).Conclusions:"Fuzheng Qingretonglin"decoction may have a protective effect on the kidney and bladder of rats with complex urinary tract infection caused by drug-resistant Escherichia coli by inhibiting the activation of NLRP3 inflammatory bodies,and TCM combined with levofloxacin has a better therapeutic effect than TCM or levofloxacin alone.

Effect of "Fuzheng Qingre Tonglin" prescription on rats with complicated urinary tract infection caused by ESBLs-producing Escherichia coli

Objective: To observe the effect of traditional Chinese medicine "Fuzheng Qingre Tonglin"prescription on rats with complicated urinary tract infection caused by extended-spectrumβ-lactamases (ESBLs)-producing Escherichia coli and its possible mechanism. Methods:Specific-pathogen-free female SD rats with 7-9 weeks old were randomly divided into model group, levofloxacin group, low-dose Fuzheng Qingre Tonglin group, high-dose Fuzheng Qingre Tonglin group, levofloxacin+Fuzheng Qingre Tonglin group (n=8 in each above group), and also there was a control group with 5 rats. Each group was administered intragastrically 2 days after model establishment for 14 consecutive days. The general condition of the rats was observed. Renal pathological changes were observed by light microscopy under hematoxylin-eosin staining. The number of white blood cells and the percentage of neutral particles (NEUT%) were detected. ELISA was used for the determination of C-reactive protein (CRP), CD4+, CD8+ in the blood, and secretory immunoglobulin A (SIgA), N-acetyl-β-D-glucosidase (NAG) molecules in urine. Results: There were a large number of inflammatory cells in the kidney of the model group and the levofloxacin group. The inflammatory cells in the treatment group were significantly reduced. The NEUT% and CRP in the blood of each treatment group and the NAG in the urine were significantly lower than those in the model group (P<0.05), except levofloxacin group. Compared with the model group, except for the levofloxacin group, serum CD4 concentration and CD4/CD8 ratio in the other treatment groups were significantly decreased, and CD8 molecules were significantly increased (P<0.05). Conclusion: "Fuzheng Qingre Tonglin" can alleviate systemic and local inflammation of complicated urinary tract infections in rats. It may also have the effect of re-sensing the insensitive antibacterial drug to bacteria and may have the function of regulating immune function and protecting kidney function in rats.