Herout Roman, Vappala Sreeparna, Hanstock Sarah, Moskalev Igor, Chew Ben H, Kizhakkedathu Jayachandran N, Lange Dirk
The Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
Department of Urology, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
Pathogens. 2023 Apr 15;12(4):604. doi: 10.3390/pathogens12040604.
Murine sepsis models are typically polymicrobial, and are associated with high mortality. We aimed to develop a high-throughput murine model that mimics a slow-paced, monomicrobial sepsis originating from the urinary tract. A total of 23 male C57Bl/6 mice underwent percutaneous insertion of a 4 mm catheter into the bladder using an ultrasound-guided method, previously developed by our group. The following day, was introduced percutaneously in the bladder in three groups: g1-50 µL 1 × 10 CFU/mL solution ( = 10); g2-50 µL 1 × 10 CFU/mL solution ( = 10); and g3 (sham mice)-50 µL sterile saline ( = 3). On day 4, mice were sacrificed. The number of planktonic bacteria in urine, adherent to catheters, and adherent to/invaded into the bladder and spleen was assessed. Cell-free DNA, D-dimer, thrombin-antithrombin complex (TAT), and 32 pro-/anti-inflammatory cytokines/chemokines were quantified in the blood. All mice survived the 4 day postinterventional period. Mean weight loss was 11% in g1, 9% in g2, and 3% in the control mice. Mean urine CFU counts were highest in group 1. All catheters showed high catheter-adhered bacterial counts. Of the infected mice, 17/20 had CFU counts in the splenic tissue, indicating septicemia. Plasma levels of cell-free DNA, D-dimer, and the proinflammatory cytokines IFN-γ, IL-6, IP-10, MIG, and G-CSF were significantly elevated in infected mice versus controls. We present a reproducible, monomicrobial murine model of urosepsis that does not lead to rapid deterioration and death, and is useful for studying prolonged urosepsis.
小鼠败血症模型通常是多微生物的，且死亡率很高。我们旨在开发一种高通量小鼠模型，该模型可模拟源自尿路的缓慢进展的单微生物败血症。总共23只雄性C57Bl/6小鼠使用我们小组先前开发的超声引导方法经皮将一根4毫米的导管插入膀胱。第二天，将以下物质经皮引入三组小鼠的膀胱中：g1组 - 50微升1×10 CFU/mL溶液（n = 10）；g2组 - 50微升1×10 CFU/mL溶液（n = 10）；g3组（假手术小鼠） - 50微升无菌盐水（n = 3）。在第4天，处死小鼠。评估尿液中浮游细菌的数量、导管上附着的细菌数量以及膀胱和脾脏上附着/侵入的细菌数量。对血液中的游离DNA、D-二聚体、凝血酶 - 抗凝血酶复合物（TAT）以及32种促炎/抗炎细胞因子/趋化因子进行定量分析。所有小鼠在干预后的4天内均存活。g1组平均体重减轻11%，g2组平均体重减轻9%，对照组小鼠平均体重减轻3%。g1组的平均尿液CFU计数最高。所有导管上的细菌附着计数都很高。在受感染的小鼠中，20只中有17只脾脏组织中的CFU计数显示存在败血症。与对照组相比，受感染小鼠血浆中的游离DNA、D-二聚体以及促炎细胞因子IFN-γ、IL-6、IP-10、MIG和G-CSF水平显著升高。我们提出了一种可重复的单微生物尿路感染败血症小鼠模型，该模型不会导致快速恶化和死亡，对于研究长期尿路感染败血症很有用。
