中药药理与临床2025，Vol.41Issue(9)：20-26,7.
蒲芩解毒利湿颗粒调控TLR4/NF-κB/NLRP3信号通路缓解大鼠慢性尿路感染
Puqin Jiedu Lishi(蒲芩解毒利湿)Granules Regulate TLR4/NF-κB/NLRP3 Signaling Pathway to Alleviate Chronic Urinary Tract Infection in Rats
摘要
Abstract
Objective:To investigate the effects of Puqin Jiedu Lishi(蒲芩解毒利湿)Granules on chronic urinary tract infection(CUTI)in rats and the possible mechanism.Methods:Escherichia coli was injected into the rat urinary tract to establish the CUTI model.SPF-grade female SD rats were randomly grouped as follows:normal control,model control,Puqin Jiedu Lishi Granules(2.03,4.05,and 8.1 g/kg),levofloxa-cin(0.036 g/kg),and levofloxacin(0.036 g/kg)+Puqin Jiedu Lishi Granules(4.05 g/kg).Each group had 10 rats and were administra-ted for 4 consecutive weeks.After administration,the urine of rats was collected for bacterial culture and counting.The ratios of bladder and kidney to body mass were calculated.The white blood cell count(WBC)and lymphocyte count(LYM)were recorded.The levels of serum creatinine(SCR)and urea nitrogen(BUN)were determined by blood biochemical assays.Serum levels of interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8),α1-microglobulin(α1-MG),immunoglobulin A(IgA),cystatin C(Cys-C),and CD4+and CD8+T cells were determined by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to ob-serve the pathological changes in the bladder and kidney tissues.The expression levels of Toll-like receptor 4(TLR4),transcription factor-κB(NF-κB)p65,and NOD receptor thermal protein domain-associated protein 3(NLRP3)were determined by immunohistochemistry and Western blot.Results:Compared with the normal control group,the model control group showed increases in the bladder index,WBC,and LYM(P<0.01),obvious pathological changes in the bladder and kidney tissues,rises in the serum levels of TNF-α,IL-6,IL-8,IL-1β,Crea,BUN,α1-MG,IgA,Cys-C,and CD8+T cells(P<0.01),reductions in the levels of CD4+T cells and CD4+/CD8+ratio(P<0.01),and up-regulated relative expression levels of TLR4,NF-κB p65,and NLRP3 in the bladder tissue(P<0.01).Compared with the model control group,the Puqin Jiedu Lishi Granules(2.03,4.05,and 8.1 g/kg),levofloxacin(0.036 g/kg),and levofloxacin(0.036 g/kg)+Puqin Jiedu Lishi Granules(4.05 g/kg)groups presented significantly improved mental state,reduced urinary frequency,relieved constipation,de-creases in the bladder index,WBC,LYM,and urine colonies(P<0.05 or P<0.01),alleviated renal tubule swelling,glomerular sac dilata-tion,bladder epithelial cell shedding,and inflammatory cell infiltration.Furthermore,the drug administration groups showed lowered levels of IL-1β,IL-6,IL-8,TNF-α,Crea,BUN,α1-MG,Cys-C,and IgA,elevated levels of CD4+T cells and CD4+/CD8+ratio(P<0.05 or P<0.01),and down-regulated relative expression levels of TLR4,NF-κB p65,and NLRP3 in the bladder tissue(P<0.05 or P<0.01).Compared with all other treatment groups,the levofloxacin+Puqin Jiedu Lishi Granules(0.036+4.05)g/kg combination markedly down-regulated the ex-pression levels of TNF-α,IL-6,IL-8,IL-1β,Crea,BUN,α1-MG,Cys-C,IgA,CD4+,TLR4,NF-κB p65 and NLRP3,and significantly ameliorated the histopathological alterations in the bladder and kidney(P<0.05 or P<0.01).Conclusion:Puqin Jidu Lishi Granules demon-strate a good therapeutic effect on CUTI in rats by inhibiting the activation of the TLR4/NF-κB/NLRP3 pathway to alleviate the inflammatory response.关键词
蒲芩解毒利湿颗粒/慢性尿路感染/炎症反应/Toll样受体4/转录因子-κB p65/NOD样受体热蛋白结构域相关蛋白3炎症小体Key words
Puqin Jiedu Lishi(蒲芩解毒利湿)Granules/Chronic urinary tract infection/Inflammatory response/Toll-like receptor 4/Tran-scription factor-κB p65/NOD-like receptor thermal protein domain-associated protein 3 inflammasome引用本文复制引用
李小凤,李喜香,葸慧荣,周亚丽..蒲芩解毒利湿颗粒调控TLR4/NF-κB/NLRP3信号通路缓解大鼠慢性尿路感染[J].中药药理与临床,2025,41(9):20-26,7.基金项目
2021年甘肃省财政转移支付地方项目(编号:20210140305) （编号:20210140305）
2023年中央财政转移支付地方项目——中药创新能力提升项目(甘财社[2023]53号). （甘财社[2023]53号）
