参照文献方法合成了S-亚硝基-N-乙酰青霉胺(SNAP)，将硅胶导管浸入SNAP溶液中，制备了SNAP导尿管，并测定了NO释放量；考察了SNAP导尿管对大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌和肺炎克雷伯菌的体外抑菌性能；采用绵羊为动物模型进行体内留置导尿管实验，考察SNAP导尿管的体内抗菌性能。结果显示：SNAP导管在第一天的NO释放量可达1.8×10-10 mol/(min·cm2)，此后NO释放量逐渐下降并可持续释放20天；SNAP导尿管对金黄色葡萄球菌具有较为明显的抑菌作用，垂直插入法和平行放置法测得的抑菌圈直径分别为2.59 mm和2.75 mm，但SNAP导尿管对其他细菌没有抑菌作用；在体内抗菌活性测定实验中，在监测17天后，在SNAP导尿管组的绵羊尿液中未检测到细菌，而在纳米银导尿管组和硅胶导尿管组的绵羊尿液中均检测出含菌量≥105 cfu/mL，表明SNAP导尿管具有较好的体内抗菌性能。
Abstract
S-nitroso-N-acetylpenicillamine (SNAP) has been synthesized according to the method described in previous literature. A silicone catheter was immersed in a SNAP solution to prepare a SNAP-impregnated catheter, and the release of NO was measured. The antibacterial properties of the SNAP catheter against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae were investigated in vitro. In vivo indwelling catheter experiments were carried out using sheep as an animal model to investigate the antibacterial properties of the SNAP catheter in vivo. NO release by the SNAP catheter reached 1.8×10-10 mol/(min·cm2) on the first day, and the NO release gradually decreased and was sustained for 20 days. The SNAP catheter had an obvious bacteriostatic effect on S. aureus, with the diameter of the bacteriostatic zone measured by the vertical insertion and parallel placement methods being 2.59 mm and 2.75 mm, respectively. The SNAP catheter had no bacteriostatic effect on other bacteria, however. In the in vivo antibacterial activity assay, after 17 days of monitoring, no bacteria were detected in the urine of sheep in the SNAP catheter group, while bacteria contents of ≥105 cfu/mL were detected in the urine of sheep in the nano-silver catheter group and the silica gel catheter group, indicating that the SNAP catheter has good in vivo antibacterial properties.
关键词
SNAP导尿管 /
抗菌性能 /
抑菌圈 /
金黄色葡萄球菌
{{custom_keyword}} /
Key words
SNAP-impregnated urinary catheter /
antibacterial property /
inhibition zone /
Staphylococcus aureus
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] KRANZ J, SCHMIDT S, WAGENLEHNER F, et al. Catheter-associated urinary tract infections in adult patients[J]. Deutsches Ärzteblatt International, 2020, 117(6): 83-88.
[2] CORTESE Y J, WAGNER V E, TIERNEY M, et al. Review of catheter-associated urinary tract infections and in vitro urinary tract models[J]. Journal of Healthcare Engineering, 2018, 2018: e2986742.
[3] FLORES-MIRELES A, HREHA T N, HUNSTAD D A. Pathophysiology, treatment, and prevention of catheter-associated urinary tract infection[J]. Topics in Spinal Cord Injury Rehabilitation, 2019, 25(3): 228-240.
[4] MAHARJAN G, KHADKA P, SIDDHI SHILPAKAR G, et al. Catheter-associated urinary tract infection and obstinate biofilm producers[J]. Canadian Journal of Infectious Diseases and Medical Microbiology, 2018, 2018: e7624857.
[5] 谷娅, 陈艺, 李子慧, 等. 留置导尿患者导尿管表面生物膜形成的危险因素分析[J]. 中国消毒学杂志, 2021, 38(11): 839-842. GU Y, CHEN Y, LI Z H, et al. Analysis of risk factors of biofilm formation on catheter surface in patients with in-dwelling urinary catheter[J]. Chinese Journal of Disinfection, 2021, 38(11): 839-842. (in Chinese)
[6] 张娟, 岳卫华. 银离子水凝胶涂层导尿管的体外抑菌效果[J]. 医疗装备, 2022, 35(1): 51-53. ZHANG J, YUE W H. In vitro evaluation of antibacterial effect of silver hydrogel coated catheter[J]. Medical Equipment, 2022, 35(1): 51-53. (in Chinese)
[7] 李育强, 智倩倩, 王晓丽, 等. 新型导尿管超滑抗菌涂层的制备及生物安全性评价[J]. 生物医学工程研究, 2019, 38(1): 105-110. LI Y Q, ZHI Q Q, WANG X L, et al. The preparation and biological safety evaluation for ultra smooth antibacterial coating for new catheter[J]. Journal of Biomedical Engineering Research, 2019, 38(1): 105-110. (in Chinese)
[8] 周小婷, 徐玉茵, 田林奇, 等. 涂层导尿管的研究进展[J]. 品牌与标准化, 2020(1): 46-50. ZHOU X T, XU Y Y, TIAN L Q, et al. Advances in the study of coated catheters[J]. Brand & Standardization, 2020(1): 46-50. (in Chinese)
[9] BRISBOIS E J, MAJOR T C, GOUDIE M J, et al. Improved hemocompatibility of silicone rubber extracorporeal tubing via solvent swelling-impregnation of S-nitroso-N-acetylpenicillamine (SNAP) and evaluation in rabbit thrombogenicity model[J]. Acta Biomaterialia, 2016, 37: 111-119.
[10] JONES M L, GANOPOLSKY J G, LABBÉ A, et al. Antimicrobial properties of nitric oxide and its application in antimicrobial formulations and medical devices[J]. Applied Microbiology and Biotechnology, 2010, 88(2): 401-407.
[11] SCHAIRER D O, CHOUAKE J S, NOSANCHUK J D, et al. The potential of nitric oxide releasing therapies as antimicrobial agents[J]. Virulence, 2012, 3(3): 271-279.
[12] LIU S X, CAI X, XUE W, et al. Chitosan derivatives co-delivering nitric oxide and methicillin for the effective therapy to the methicillin-resistant S. aureus infection[J]. Carbohydrate Polymers, 2020, 234: 115928.
[13] WU M, LU Z H, WU K K, et al. Recent advances in the development of nitric oxide-releasing biomaterials and their application potentials in chronic wound healing[J]. Journal of Materials Chemistry B, 2021, 9(35): 7063-7075.
[14] COLLETTA A, WU J, WO Y, et al. S-nitroso-N-acetylpenicillamine (SNAP) impregnated silicone foley catheters: a potential biomaterial/device to prevent catheter-associated urinary tract infections[J]. ACS Biomaterials Science & Engineering, 2015, 1(6): 416-424.
[15] WO Y, LI Z, BRISBOIS E J, et al. Origin of long-term storage stability and nitric oxide release behavior of CarboSil polymer doped with S-nitroso-N-acetyl-D-penicillamine[J]. ACS Applied Materials & Interfaces, 2015, 7(40): 22218-22227.
[16] CHIPINDA I, SIMOYI R H. Formation and stability of a nitric oxide donor: S-nitroso-N-acetylpenicillamine[J]. The Journal of Physical Chemistry B, 2006, 110(10): 5052-5061.
[17] WO Y, BRISBOIS E J, WU J, et al. Reduction of thrombosis and bacterial infection via controlled nitric oxide (NO) release from S-nitroso-N-acetylpenicillamine (SNAP) impregnated CarboSil intravascular catheters[J]. ACS Biomaterials Science & Engineering, 2017, 3(3): 349-359.
[18] 李非，马艳斌，迟戈. 基于技术审评的一次性使用导尿管研究[J]. 中国医疗器械信息,2010,16(9):40-43. LI F, MA Y B, CHI G. Research of catheters based on medical device evaluation[J]. China Medical Device Information, 2010, 16(9): 40-43. (in Chinese)
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
湖北省重点研发计划项目(社会发展领域)(2022BCA018)
{{custom_fund}}
PDF(3535 KB)
