头孢他啶纳米粒包被导管对铜绿假单胞菌介导小鼠导管相关性尿路感染的影响

Effect of ceftazidime nanoparticles coated-catheters on Pseudomonas aeruginosa-mediated catheter-associated urinary tract infection in mice

目的探讨头孢他啶(CAZ)纳米粒包被导管对铜绿假单胞菌引起的导管相关性尿路感染(CAUTI)的影响,为CAUTI治疗提供理论依据。方法采用高效液相色谱法测定CAZ纳米粒的药物含量,平板扩散法测定纳米粒包被导管的体外抑菌活性,菌落平板计数法测定小鼠膀胱组织和导管表面的细菌数,苏木素-伊红(HE)染色观察小鼠膀胱组织病理特征,酶联免疫吸附试验(ELISA)测定膀胱组织炎症细胞因子水平。结果CAZ纳米粒包被导管表面可以持续释放药物,且在体外具有较长的抗菌活性。铜绿假单胞菌介导小鼠CAUTI模型结果显示,CAZ纳米粒包被导管表面生物膜形成量较未包被的导管显著降低(P<0.01);CAZ处理组(小鼠体内植入CAZ纳米粒包被导管)小鼠膀胱组织细菌数较空白对照组(小鼠体内植入未包被的导管)也显著降低(P<0.01)。CAZ处理组小鼠膀胱组织上皮细胞有部分脱落和轻微炎症,但未发现有空白对照组所表现的上皮细胞大量脱落坏死、水肿及中性粒细胞浸润等严重炎症。此外,CAZ处理组膀胱组织IL-6和TNF-α水平显著低于空白对照组,而IL-10水平显著高于空白对照组(P<0.01)。结论CAZ纳米粒包被导管通过在体内释放有效的药物浓度可防止铜绿假单胞菌的黏附和生物膜形成。

Objective To investigate the effect of urinary catheters coated with ceftazidime(CAZ)nanoparticles on catheter-associated urinary tract infection(CAUTI)caused by Pseudomonas aeruginosa(P.aeruginosa),and provide a theoretical basis for clinical treatment of CAUTI.Methods The drug content of CAZ nanoparticles was determined by high performance liquid chromatography,the antibacterial activity of CAZ nanoparticles-coated catheter was measured by plate diffusion method,the bacterial number of bladder tissue in murine and the implant′s surface was determined by colony plate counting method.HE staining was used to observe the pathological features of bladder tissues.ELISA method was used to determine the level of inflammatory cytokines in bladder tissue.Results The surface of catheter coated with CAZ nanoparticles could release drug continuously and had a longer antibacterial activity in vivo.The results of P.aeruginosa-mediated CAUTI in the murine model showed that the biofilm formation on the surface of catheters coated with CAZ nanoparticles and the number of bacteria in the bladder tissue were significantly reduced when compared with catheters coated without CAZ nanoparticles(P<0.01).In the CAZ nanoparticles-coated group(mice implanted with catheters coated with CAZ nanoparticles),there was partial shedding of the bladder epithelial cells and slight inflammation,but the severe inflammation such as loss and necrosis of many epithelial cells,edema and neutrophil infiltration which present in the uncoated control group(mice implanted with catheters coated without CAZ nanoparticles)was not observed.In addition,the levels of IL-6 and TNF-αin the bladder tissue in the CAZ nanoparticles-coated group were significantly lower than those in the uncoated control group,while the IL-10 level was significantly higher than that in the uncoated control group(P<0.01).Conclusion CAZ nanoparticles-coated catheters prevent the adhesion and biofilm formation of P.aeruginosa by releasing effective drug concentrations in vivo.