收稿日期: 2026-01-19
网络出版日期: 2026-06-15
基金资助
山东省自然科学基金项目(ZR2021MH329);济南市科技创新发展资金项目(202430025)
The relationship between iNOS, CER and NLRP3/IL-1β signal pathway and urinary tract infection after bladder cancer operation
Received date: 2026-01-19
Online published: 2026-06-15
目的 探讨诱导型一氧化氮合酶(iNOS)、铜蓝蛋白(CER)及Nod样受体蛋白3(NLRP3)/白细胞介素-1β(IL-1β)信号通路与膀胱癌术后尿路感染的关系。 方法 选取2020年8月至2025年8月山东第一医科大学附属人民医院收治的102例膀胱癌术后尿路感染患者作为尿路感染组,同期选取膀胱癌术后无尿路感染患者102例作为无尿路感染组。分析膀胱癌术后尿路感染患者病原菌分布,比较两组临床资料、iNOS、CER及NLRP3/IL-1β信号通路,予以多因素logistic回归分析法分析膀胱癌术后尿路感染的影响因素,并采用受试者工作特征(ROC)曲线分析血清iNOS、CER及NLRP3/IL-1β信号通路对膀胱癌术后尿路感染的评估价值。 结果 102例膀胱癌术后尿路感染患者共培养出128株病原菌,占比较高的主要为大肠埃希菌和肺炎克雷伯菌,占比分别为37.50%、17.97%。尿路感染组年龄高于无尿路感染组,合并高血压、合并糖尿病、肿瘤分期为Ⅲ期/Ⅳ期、手术时间> 360 min、术后留置导管时间> 7 d的患者占比均高于无尿路感染组(P < 0.05)。尿路感染组血清iNOS、CER、IL-1β、外周血NLRP3水平均高于无尿路感染组(P < 0.05)。多因素logistic回归分析结果显示,年龄偏高、合并糖尿病、手术时间> 360 min、术后留置导管时间> 7 d、血清iNOS水平偏高、血清CER水平偏高、外周血NLRP3 mRNA表达偏高、血清IL-1β水平偏高是膀胱癌术后尿路感染的独立危险因素(OR = 1.881、4.773、1.458、6.322、3.640、2.442、1.594、3.677,P < 0.05)。将尿路感染组纳入阳性,无尿路感染组纳入阴性,血清iNOS、CER及NLRP3/IL-1β信号通路及联合检测评估膀胱癌术后尿路感染的曲线下面积(AUC)分别为0.713、0.736、0.753、0.747、0.939,其中联合检测的AUC最高(P < 0.05)。 结论 大肠埃希菌和肺炎克雷伯菌为膀胱癌术后尿路感染患者主要感染的病原菌,年龄偏高、合并糖尿病、手术时间> 360 min、术后留置导管时间> 7 d、血清iNOS水平偏高、血清CER水平偏高、外周血NLRP3 mRNA表达偏高、血清IL-1β水平偏高是膀胱癌术后尿路感染的独立影响因素,血清iNOS、CER及NLRP3/IL-1β信号通路联合对膀胱癌术后尿路感染具有较高评估价值。
关键词: 膀胱癌; 尿路感染; 诱导型一氧化氮合酶; 铜蓝蛋白; Nod样受体蛋白3/白细胞介素-1β信号通路
吕涛 , 陶冉 , 张敏 , 吕昌敏 , 孟庆荣 , 王世平 . iNOS、CER及NLRP3/IL-1β信号通路与膀胱癌术后尿路感染的关系[J]. 实用医学杂志, 2026 , 42(11) : 2056 -2063 . DOI: 10.3969/j.issn.1006-5725.2026.11.021
Objective To investigate the relationship between inducible nitric oxide synthase (iNOS), ceruloplasmin (CER), and the Nod-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway and urinary tract infection after bladder cancer surgery. Methods From August 2020 to August 2025, 102 patients who developed urinary tract infection after bladder cancer surgery and were admitted to the People's Hospital Affiliated to Shandong First Medical University were selected as the urinary tract infection group. Meanwhile, 102 patients who did not develop urinary tract infection after bladder cancer surgery during the same period were selected as the non-urinary tract infection group. The distribution of pathogenic bacteria in patients with urinary tract infection after bladder cancer surgery was analyzed. The clinical data, iNOS, CER, and the NLRP3/IL-1β signaling pathway were compared between the two groups. The influencing factors of urinary tract infection after bladder cancer surgery were analyzed using multivariate logistic regression analysis. The evaluation value of serum iNOS, CER, and the NLRP3/IL-1β signaling pathway for urinary tract infection after bladder cancer surgery was analyzed by the receiver operating characteristic (ROC) curve. Results A total of 128 strains of pathogenic bacteria were cultured from 102 patients with urinary tract infection following bladder cancer surgery. Escherichia coli and Klebsiella pneumoniae accounted for 37.50% and 17.97% respectively. The age of the urinary tract infection group was greater than that of the non-urinary tract infection group. Moreover, the proportion of patients with hypertension, diabetes, tumor stage Ⅲ/Ⅳ, operation duration > 360 min, and postoperative indwelling catheter time > 7 d was higher in the urinary tract infection group than in the non-urinary tract infection group (P < 0.05). The levels of serum iNOS, CER, IL-1β, and peripheral blood NLRP3 in patients with urinary tract infection were higher than those in patients without urinary tract infection (P < 0.05). Multivariate logistic regression analysis indicated that advanced age, diabetes mellitus, operation duration > 360 min, postoperative indwelling catheter time > 7 d, elevated serum iNOS level, elevated serum CER level, increased peripheral blood NLRP3 mRNA expression, and elevated serum IL-1β level were independent influencing factors of urinary tract infection after bladder cancer surgery (OR = 1.881, 4.773, 1.458, 6.322, 3.640, 2.442, 1.594, 3.677, P < 0.05). The urinary tract infection group was considered as positive, while the non-urinary tract infection group was considered as negative. The areas under the curve (AUC) of serum iNOS, CER, NLRP3/IL-1β signaling pathway, and combined detection for evaluating urinary tract infection after bladder cancer surgery were 0.713, 0.736, 0.753, 0.747, and 0.939 respectively, and the AUC of combined detection was the highest (P < 0.05). Conclusions Escherichia coli and Klebsiella pneumoniae were identified as the primary pathogens responsible for urinary tract infections following bladder cancer surgery. Advanced age, diabetes, an operation duration exceeding 360 minutes, a postoperative indwelling catheter time longer than 7 days, elevated serum iNOS levels, high serum CER levels, increased peripheral blood NLRP3 mRNA expression, and elevated serum IL-1β levels were determined to be independent influencing factors for urinary tract infections after bladder cancer surgery. The combination of serum iNOS, CER, and the NLRP3/IL-1β signaling pathway exhibited high evaluation value for urinary tract infections after bladder cancer surgery.
| [1] | 蔡令凯, 杨潇, 谈政烨, 等. NeoVI-RADS评分在膀胱癌新辅助治疗患者中的应用研究[J]. 中华外科杂志, 2025, 63(12): 1111-1117. doi: 10.3760/cma.j.cn112139-20250326-00160 . |
| [2] | NAM K C, PARK B J. Antibacterial and anticancer activity of multifunctional iron-based magnetic nanoparticles against urinary tract infection and cystitis-related bacterial strains and bladder cancer cells[J]. Biomed Eng Lett, 2025, 15(5): 1-13. doi: 10.1007/s13534-025-00489-1 . |
| [3] | SAHU D, HUAN J, WANG H, et al. Bladder Cancer Invasion is Mediated by mTORC2-Driven Regulation of Nitric Oxide and Invadopodia Formation[J]. Am J Pathol, 2021, 191(12): 2203-2218. doi: 10.1016/j.ajpath.2021.08.002 . |
| [4] | MUKAE Y, ITO H, MIYATA Y, et al. Ceruloplasmin Levels in Cancer Tissues and Urine Are Significant Biomarkers of Pathological Features and Outcome in Bladder Cancer[J]. Anticancer Res, 2021, 41(8): 3815-3823. doi: 10.21873/anticanres.15174 . |
| [5] | XU G, HUANG R, XIA W, et al. Associations between inflammasome-related gene NLRP3 Polymorphisms (rs10754558 and rs35829419) and risk of bladder cancer in a Chinese population[J]. J Clin Lab Anal, 2021, 35(11): e23973. doi: 10.1002/jcla.23973 . |
| [6] | 陈孝平, 汪建平, 赵继宗. 外科学[M]. 9版. 北京: 人民卫生出版社, 2018: 535-540, 569-570. doi:10.3877/cma.j.issn.1674-3946.2018.05.001 |
| [7] | 中华人民共和国卫生部. 医院感染诊断标准(试行)[J]. 中华医学杂志, 2001, 81(5): 314-320. doi: 10.3760/j:issn:0376-2491.2001.05 . |
| [8] | 尚红, 王毓三, 申子瑜. 全国临床检验操作规程[M]. 4版. 北京: 人民卫生出版社, 2015: 624-692. |
| [9] | 尤琴琴, 俞飞, 李如帅, 等. 18F-FDG PET/MR及其衍生参数在膀胱癌诊断与分期中的应用[J]. 中华核医学与分子影像杂志, 2025, 45(7): 405-410. doi: 10.3760/cma.j.cn321828-20250204-00027 . |
| [10] | 刘志聪, 刘戴胤, 龙钧天, 等. 外泌体lncRNA CIAT1促进膀胱癌集体侵袭的机制[J]. 实用医学杂志, 2025, 41(9): 1299-1308. doi: 10.3969/j.issn.1006-5725.2025.09.005 . |
| [11] | MICHAEL C, LAURA L, ELIJAH W, et al. Comparing concentration of urinary inflammatory cytokines in interstitial cystitis, overactive bladder, urinary tract infection, and bladder cancer[J]. Urological Science, 2022, 33(4): 199-204. doi: 10.1016/j.biopha.2022.113433 . |
| [12] | 孙晓宇,方程,李晓阳,等. 1990~2021年全球膀胱癌疾病负担趋势分析及2050年预测:一项基于GBD 2021的系统分析.中华腔镜泌尿外科杂志(电子版),2026,20(1) : 34-43. DOI: 10.3877/cma.j.issn.1674-3253.2026.01.005 |
| [13] | LARSEN E S, JOENSEN U N, POULSEN A M, et al. Bacillus Calmette-Guérin immunotherapy for bladder cancer: A review of immunological aspects, clinical effects and BCG infections[J]. APMIS, 2020, 128(2): 92-103. doi: 10.1111/apm.13011 . |
| [14] | LI J, PARK A, FULMER B R, et al. Leclercia adecarboxylata urinary tract infection in a patient with bladder cancer and recurrent hematuria[J]. Urol Case Rep, 2021, 36: 101579. doi: 10.1016/j.eucr.2021.101579 . |
| [15] | 陈怡, 陈沛林, 吕晓磊, 等. 膀胱癌尿路感染患者免疫和炎症因子的表达及临床诊断价值[J]. 中华医院感染学杂志, 2022, 32(1): 80-84. doi: 10.11816/cn.ni.2022-210414 . |
| [16] | 李瑜, 满晓军. 非肌层浸润性膀胱癌患者经尿道膀胱肿瘤切除术后发生膀胱痉挛的影响因素[J]. 中国医科大学学报, 2022, 51(5): 425-428. doi: 10.12007/j.issn.0258-4646.2022. 05.008 . |
| [17] | 王晓寒, 杜鹏飞, 屈晓东, 等. 非肌层浸润性膀胱癌患者TURBT术后并发尿路感染危险因素及预测模型构建[J]. 中华医院感染学杂志, 2023, 33(7): 1071-1075. doi: 10.11816/cn.ni.2023-221315 . |
| [18] | 薛笑楠, 郑伟坤, 官雯娟, 等. 2型糖尿病并发尿路感染病原学和耐药性及其危险因素[J]. 中华医院感染学杂志, 2024, 34(5): 703-706. doi: 10.11816/cn.ni.2024-231119 . |
| [19] | 金婷婷, 李云娇, 高凤蕊, 等. 根治性膀胱切除术后尿路感染病原学及外周血TLR4/NF-κB信号通路[J]. 中华医院感染学杂志, 2023, 33(24): 3753-3757. doi: 10.11816/cn.ni.2023-230585 . |
| [20] | 黄家望, 马心悦, 冯芷莹, 等. A型流感病毒通过激活HIF-1α/iNOS/VEGF信号通路诱导肺上皮细胞铁死亡的机制[J]. 微生物学通报, 2024, 51(1): 306-322. doi: 10.13344/j.microbiol.china.230433 . |
| [21] | BELGOROSKY D, GIROUARD J, LANGLE Y V, et al. Relevance of iNOS expression in bladder cancer stem cells[J]. J Mol Med (Berl), 2021, 81(13): 1615-1627. doi: 10.1007/s00109-020-01973-0 . |
| [22] | KANG N L, ZHANG J M, LIU Y R, et al. Novel predictive models using serum ceruloplasmin levels for hepatic steatosis in patients with chronic hepatitis B infection[J]. Clin Res Hepatol Gastroenterol, 2020, 44(1): 57-65. doi: 10.1016/j.clinre.2019. 04.001 . |
| [23] | BAISHAN A, AIKEBAIER A, DILIMULATI D, et al. Bioinformatics Analysis of the Anti-Inflammatory Mechanism and Potential Therapeutic Efficacy of Kezimuke granules in Treating Urinary Tract Infections by Inhibiting NLRP3 Inflammasome Activation[J]. Int J Mol Sci, 2025, 26(4): 1764. doi: 10.3390/ijms 26041764 . |
| [24] | PAUDEL S, KUMAR R, ROGERS A K, et al. The NLRP3 Inflammasome Is Dispensable in Methicillin-Resistant Staphylococcus aureus Urinary[J]. Pathogens, 2024, 13(2): 106-106. doi: 10.3390/pathogens13020106 . |
| [25] | 闫红霞, 马磊, 颜彦, 等. 重症肺炎多重耐药菌感染危险因素及NLRP3/IL-1β的预测价值[J]. 中华医院感染学杂志, 2024, 34(6): 812-815. doi: 10.11816/cn.ni.2024-231086 . |
| [26] | 孙小丽, 申永辉, 刘军云, 等. 精神分裂症患者尿路感染病原菌及外周血NLRP3/IL-1β通路表达[J]. 中华医院感染学杂志, 2024, 34(22): 3417-3421. doi: 10.11816/cn.ni.2024-240176 . |
| [27] | MOREIRA J D, IAKHIAEV A, VANKAYALAPATI R, et al. Histone deacetylase-2 controls IL-1β production through the regulation of NLRP3 expression and activation in tuberculosis infection[J]. iScience, 2022, 25(8): 104799. doi: 10.1016/j.isci. 2022.104799 . |
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