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局部应用辛伐他汀可促进金黄色葡萄球菌污染的皮肤伤口愈合。

Topical simvastatin promotes healing of Staphylococcus aureus-contaminated cutaneous wounds.

机构信息

School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.

PhD Program of Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

Int Wound J. 2016 Dec;13(6):1150-1157. doi: 10.1111/iwj.12431. Epub 2015 Mar 8.

Abstract

Cutaneous wounds are prompt to be contaminated by bacteria, but the clinical benefits of applying antibiotics and antiseptics in wound management have not been proven. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors commonly used to lower cholesterol levels. Studies indicated that statins, especially simvastatin, promote wound healing in experimental models. As Staphylococcus aureus is one of the most important microorganism responsible for wound infections, the aims of this study were to characterise the anti-staphylococcal activity of simvastatin and to evaluate the application of simvastatin as a topical therapy for S. aureus-contaminated wounds. In the present study, simvastatin was bacteriostatic against S. aureus at sub-inhibitory concentrations up to 8 hours after exposure. Further increased concentrations of simvastatin above the minimal inhibitory concentration (MIC) did not enhance the growth inhibitory effect. By contrast, the ability of simvastatin to inhibit S. aureus biofilm formation was concentration dependent. Topical application of simvastatin at its MIC against S. aureus accelerated the healing and bacterial clearance of S. aureus-contaminated wounds in an excisional mice wound model. This effective concentration is well below the safe concentration for topical use. Collectively, topical application of simvastatin has the potential as a novel modality for managing wound infections and promoting wound healing.

摘要

皮肤创伤容易受到细菌污染,但在伤口管理中应用抗生素和消毒剂的临床益处尚未得到证实。他汀类药物是常用的降低胆固醇水平的 3-羟基-3-甲基戊二酰基辅酶 A(HMG-CoA)还原酶抑制剂。研究表明,他汀类药物,特别是辛伐他汀,可促进实验模型中的伤口愈合。由于金黄色葡萄球菌是导致伤口感染的最重要微生物之一,本研究旨在研究辛伐他汀的抗葡萄球菌活性,并评估辛伐他汀作为治疗金黄色葡萄球菌污染伤口的局部治疗方法的应用。在本研究中,辛伐他汀在暴露后长达 8 小时的亚抑制浓度下对金黄色葡萄球菌具有抑菌作用。高于最小抑菌浓度(MIC)的辛伐他汀浓度进一步增加不会增强抑菌效果。相比之下,辛伐他汀抑制金黄色葡萄球菌生物膜形成的能力与浓度相关。辛伐他汀在其 MIC 下局部应用于金黄色葡萄球菌可加速金黄色葡萄球菌污染创面的愈合和细菌清除,在切除小鼠创面模型中。这种有效浓度远低于局部使用的安全浓度。总之,局部应用辛伐他汀有可能成为治疗伤口感染和促进伤口愈合的新方法。

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