树鼩细菌感染模型的建立及抗菌药物的治疗效果评价(英文)

在抗微生物感染药物开发过程中, 动物模型是必不可少的。虽然目前已经用啮齿类动物建立了一些细菌感染动物模型, 但在小型灵长类动物中还很少见。这里首次报道两个树鼩细菌感染动物模型。第一种是在三度烫伤后的皮肤表面接种 5×106 CFU 的金黄色葡萄球菌构建的皮肤烫伤感染模型。这个数量的金黄色葡萄球菌可以造成 7 d 持续性感染, 并且在第 4天可以看到明显的炎症反应。第二种是用绿脓杆菌构建的涤纶补片感染模型, 接种 2×106 CFU 的绿脓杆菌同样可以引起持续 6 d 感染, 并在第三天在伤口处观察到大量的脓液。进一步用这两种模型评价头孢哌酮钠和左氧氟沙星的治疗效果。左氧氟沙星和头孢哌酮钠在皮肤烫伤感染模型中能分别将 100 mg 皮肤组织中的细菌降低到 4log10 和 5log10 CFU, 并且在涤纶补片植入感染模型中这两种抗生素都能显著地将感染的细菌降低了 4log10 CFU (P<0.05)。结果表明用金黄色葡萄球菌和绿脓杆菌成功构建了两个细菌感染的树鼩模型。此外, 树鼩对金黄色葡萄球菌和绿脓杆菌很敏感, 适合用于构建细菌感染动物模型和评价新的抗细菌感染药物的效果。

Two bacterial infection models in tree shrew for evaluating the efficacy of antimicrobial agents

Animal models are essential for the development of new anti-infectious drugs. Although some bacterial infection models have been established in rodents, small primate models are rare. Here, we report on two bacterial infection models established in tree shrew (Tupaia belangeri chinensis). A burnt skin infection model was induced by dropping 5×10⁶ CFU of Staphylococcus aureus on the surface of a wound after a third degree burn. This dose of S. aureus caused persistent infection for 7 days and obvious inflammatory response was observed 4 days after inoculation. A Dacron graft infection model, 2×10⁶ CFU of Pseudomonas aeruginosa also caused persistent infection for 6 days, with large amounts of pus observed 3 days after inoculation. These models were used to evaluate the efficacy of levofloxacin (LEV) and cefoperazone (CPZ), which reduced the viable bacteria in skin to 4log₁₀ and 5log₁₀ CFU/100 mg tissue, respectively. The number of bacteria in graft was significantly reduced by 4log₁₀ CFU/mL treatment compared to the untreated group (P<0.05). These results suggest that two bacterial infection models were successfully established in tree shrew using P. aeruginosa and S. aureus. In addition, tree shrew was susceptible to P. aeruginosa and S. aureus, thus making it an ideal bacterial infection animal model for the evaluation of new antimicrobials.