Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model.
Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model.
复制标题
在生物膜挑战的糖尿病小鼠模型中伤口愈合延迟伤口愈合的时间过程。
DOI：
10.1111/j.1524-475x.2012.00793.x
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Olerud JE
中科院分区：
文献类型：
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作者：
Zhao G;Usui ML;Underwood RA;Singh PK;James GA;Stewart PS;Fleckman P;Olerud JE
细菌生物膜已被证明在延迟慢性伤口的伤口愈合方面发挥作用，这是一个重大的医疗问题，导致重大的医疗负担。一种可重复性的动物模型对研究慢性创面的机制和处理具有重要价值。我们以前的工作表明，铜绿假单胞菌(PAO1)生物膜对糖尿病(db/db)小鼠创面的攻击显著延迟了创面的愈合。在这项创伤时间进程研究中，我们进一步研究了PAO1生物膜攻击db/db小鼠模型的细菌负荷、伤口愈合延迟和宿主炎症反应的某些方面。将PAO1生物膜转移到db/db小鼠背部2天龄创面上。无生物膜对照创面4周愈合，与前人研究一致；生物膜创面4周无一愈合；%生物膜创面6周愈合；所有生物膜创面8周愈合。在伤口愈合过程中，铜绿假单胞菌逐渐从伤口中清除，而金黄色葡萄球菌(正常小鼠皮肤菌群的一部分)的存在增加。所有未愈合伤口的结痂中含有107株铜绿假单胞菌，比从伤口床分离出的铜绿假单胞菌数量高出100倍(即99%的铜绿假单胞菌在结痂内)。组织学和遗传学分析显示表皮增生，血管生成不足，炎性细胞因子增加。低氧诱导因子(HIF)在4周创面表达增加3倍。总之，我们的研究表明，生物膜挑战的伤口通常在大约6周内愈合，比非生物膜挑战的正常伤口至少多2周。这些数据表明，这种延迟伤口愈合的模型可以在体内研究细菌生物膜对宿主防御的反应以及生物膜对宿主伤口愈合途径的影响。它也可以用来测试抗生物膜策略，治疗慢性伤口.
Bacterial biofilm has been shown to play a role in delaying wound healing of chronic wounds, a major medical problem that results in significant healthcare burden. A reproducible animal model could be very valuable for studying the mechanism and management of chronic wounds. Our previous work demonstrated that Pseudomonas aeruginosa (PAO1) biofilmchallenge on wounds in diabetic (db/db) mice significantly delayed wound healing. In this wound time course study, we further characterize the bacterial burden, delayed wound healing and certain aspects of the host inflammatory response in the PAO1 biofilm-challenged db/db mouse model. PAO1 biofilms were transferred onto 2 day old wounds created on the dorsal surface of db/db mice. Control wounds without biofilm-challenge healed by 4 weeks, consistent with previous studies; none of the biofilm-challenged wounds healed by 4 weeks; 64% of the biofilm-challenged wounds healed by 6 weeks; and all of the biofilm-challenged wounds healed by 8 weeks. During the wound healing process, P. aeruginosa were gradually cleared from the wounds while the presence of S. aureus (part of the normal mouse skin flora) increased. Scabs from all unhealed wounds contained 107 P. aeruginosa, which was 100 fold higher than the counts isolated from wound beds (i.e. 99% of the P. aeruginosa was in the scab). Histology and genetic analysis showed proliferative epidermis, deficient vascularization and increased inflammatory cytokines. Hypoxia inducible factor (HIF) expression increased 3 fold in 4 week wounds. In summary, our study demonstrates that biofilm-challenged wounds typically heal in approximately 6 weeks, at least 2 weeks longer than non biofilm-challenged normal wounds. These data suggest that this delayed wound healing model enables the in vivo study of bacterial biofilm responses to host defenses and the effects of biofilms on host wound healing pathways. It may also be used to test anti-biofilm strategies the treatment of chronic wounds.