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替加环素通过调节基质金属蛋白酶-9加速葡萄球菌感染性烧伤创面愈合。

Tigecycline accelerates staphylococcal-infected burn wound healing through matrix metalloproteinase-9 modulation.

机构信息

Department of Dermatology, Università Politecnica delle Marche, Ancona, Italy.

出版信息

J Antimicrob Chemother. 2012 Jan;67(1):191-201. doi: 10.1093/jac/dkr440. Epub 2011 Nov 6.

DOI:10.1093/jac/dkr440
PMID:22065244
Abstract

OBJECTIVES

We investigated the in vivo efficacy of tigecycline, a new glycylcycline (a tetracycline derivative), in the management of methicillin-resistant Staphylococcus aureus (MRSA)-infected experimental surgical wounds in rats. The main outcome measures were quantitative bacterial culture, histological examination and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9) and collagen IV.

METHODS

An animal model was used to compare the in vivo efficacy of teicoplanin and tigecycline in the treatment of burn wound infections by S. aureus. A copper bar, heated in boiling water, was placed on the paraspinal site of each rat, resulting in full thickness burns. A small gauze was placed over each burn and then inoculated with 5 × 10(7) cfu of S. aureus ATCC 43300. To mimic the clinical situation in burn patients, surgical debridement was performed 48 h after the injury. The wounds were left to heal by secondary intention. The study included an uninfected control group that did not receive any treatment, a contaminated group that did not receive any treatment, and two contaminated groups treated with intraperitoneal tigecycline (2 mg/kg) and teicoplanin (7 mg/kg), respectively.

RESULTS

All antibiotic treatments were significantly effective. Tigecycline showed the highest antimicrobial activity, with a better impact on histological results. Infected rats treated with tigecycline showed a significant decrease in MMP-9 expression both in epithelium and in dermis compared with rats treated with teicoplanin.

CONCLUSIONS

Tigecycline, besides its antimicrobial activity, exerts an important modulatory effect on MMP-9, accelerating wound healing in staphylococcal-infected burns.

摘要

目的

我们研究了新型甘氨酰环素(四环素衍生物)替加环素治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染实验性大鼠外科手术伤口的体内疗效。主要观察指标是定量细菌培养、组织学检查和基质金属蛋白酶-9(MMP-9)和 IV 型胶原的免疫组织化学表达。

方法

采用动物模型比较替考拉宁和替加环素治疗金黄色葡萄球菌烧伤感染的体内疗效。将一根在沸水中加热的铜棒置于每只大鼠的脊柱旁部位,造成全层烧伤。在每个烧伤部位放置一小片纱布,然后接种 5×10(7)cfu 的金黄色葡萄球菌 ATCC 43300。为了模拟烧伤患者的临床情况,在损伤后 48 小时进行外科清创术。伤口让其二期愈合。研究包括一个未感染的对照组,即未接受任何治疗;一个污染组,即未接受任何治疗;两个污染组分别接受腹腔内替加环素(2mg/kg)和替考拉宁(7mg/kg)治疗。

结果

所有抗生素治疗均有显著疗效。替加环素显示出最高的抗菌活性,对组织学结果的影响更好。与用替考拉宁治疗的感染大鼠相比,用替加环素治疗的大鼠上皮和真皮中的 MMP-9 表达明显降低。

结论

替加环素除了具有抗菌活性外,还对 MMP-9 具有重要的调节作用,可加速金黄色葡萄球菌感染烧伤的伤口愈合。

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