金黄色葡萄球菌性骨髓炎动物模型构建的研究与进展

Research progress in constructing animal models of Staphylococcus aureus-associated osteomyelitis

背景:金黄色葡萄球菌已成为目前全世界骨髓炎最主要的致病菌。优秀而标准的同质性动物模型对骨髓炎感染机制的研究、获得新的预防与治疗措施及新技术转化应用于临床实践的科学研究具有重要作用。目的:综述国内外金黄色葡萄球菌性骨髓炎动物模型构建的相关研究进展及面临的问题。方法:计算机检索CNKI数据库、PubMed数据库、MEDLINE数据库、Embase数据库、Cochrane图书馆的相关文献,中文检索词为"金黄色葡萄球菌;骨感染;骨髓炎;置入物相关骨髓炎;骨缺损骨髓炎;骨折骨髓炎;生物膜;实验性骨髓炎模型;动物模型";英文检索词为"Staphylococcus aureus;bone infection;osteomyelitis;implant-associated osteomyelitis;bone defect osteomyelitis;fracture osteomyelitis;biofilm;experimental osteomyelitis model"。语言分别设为中文和英文。查阅2010年1月至2019年6月期间收录的相关文章,包括综述、基础研究以及临床研究。通过阅读文题和摘要进行初步筛选,排除与文章主题不相关的文献,根据纳入标准和排除标准,最终纳入45篇文献进行结果分析。结果与结论:①骨髓炎动物模型的构建方法与多种因素有关,尽管近年来各国研究者对此不断进行改进并逐渐量化感染过程,但尚未形成统一标准;②目前并无单一微生物学或影像学检查方式能明确骨感染,在急性骨髓炎动物模型中,nuc RTQ-PCR技术和生物荧光成像技术等微生物学检测能够早期动态监测并量化骨感染过程;对于慢性骨髓炎动物模型,micro-CT、MRI等影像学技术能动态观察骨溶解、骨重建过程,且18F-FDG PET/CT等尖端成像技术确认或排除慢性骨髓炎有很高的诊断准确性;③基于骨髓炎动物模型,确定早期诊断及量化诊疗过程中感染细菌数量及活性的标准,也是今后进一步研究的方向。

BACKGROUND:Staphylococcus aureus has become the most important pathogen of osteomyelitis in the world.An excellent and standard homogenous animal model plays an important role regarding the infectious mechanism of osteomyelitis,the acquisition of new preventive and therapeutic measures,and the application of new technologies in clinical practice.OBJECTIVE:To review the research progress and problems in the construction of animal models of Staphylococcus aureus-associated osteomyelitis at home and abroad.METHODS:A computer-based search of CNKI,PubMed,MEDLINE,Embase,and Cochrane was performed for relevant articles concerning the experimental osteomyelitis model,including review,basic research and clinical research,published from January 2010 to June 2019.The keywords were"Staphylococcus aureus;bone infection;osteomyelitis;implant-associated osteomyelitis;bone defect osteomyelitis;fracture osteomyelitis;biofilm;experimental osteomyelitis model"in Chinese and English,respectively.After initial screening of titles and abstracts and exclusion of irrelevant articles,45 eligible articles were included in final analysis.RESULTS AND CONCLUSION:Construction of an osteomyelitis animal model is related to many factors.Although researchers from various countries have continuously improved and gradually quantified the infection process in recent years,a unified standard has not yet been developed.To date,there is no single microbiology or imaging method to determine bone infection.In animal models of acute osteomyelitis,the use of microbiological tests such as nuc RTQ-PCR and bioluminescence tomography can dynamically monitor and quantify the bone infection process at an early stage.In the animal model of chronic osteomyelitis,we can dynamically observe the process of osteolysis and bone remodeling based on the micro-CT and MRI images.Advanced imaging technologies such as 18 F-FDG PET/CT can be used to confirm or exclude chronic osteomyelitis with high diagnostic accuracy.The use of animal models of osteomyelitis contributes to standardizing the number and activity of infected bacteria during early diagnosis and quantified treatment,which is the direction for further research.