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抗菌光动力疗法联合抗生素治疗大鼠三度烧伤

Antimicrobial Photodynamic Therapy Combined With Antibiotic in the Treatment of Rats With Third-Degree Burns.

作者信息

Zhao Zhanjuan, Ma Jinduo, Wang Yiyi, Xu Zehua, Zhao Lu, Zhao Jianxi, Hong Ge, Liu Tianjun

机构信息

College of Basic Medicine, Hebei University, Baoding, China.

Tianjin Key Laboratory of Biomedical Material, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

出版信息

Front Microbiol. 2021 Feb 24;12:622410. doi: 10.3389/fmicb.2021.622410. eCollection 2021.

Abstract

Cationic porphyrin conjugate, protoporphyrin IX-methyl ethylenediamine derivative (PPIX-MED) has a potent photosensitive antibacterial effect on clinically isolated bacteria, including methicillin-resistant , (MRSA), , and . This study investigated (i) the PPIX-MED-mediated antimicrobial photodynamic effect on these three species and (ii) the effect of antimicrobial photodynamic therapy (aPDT) combined with the use of an antibiotic on the healing of third-degree burns of rats with the wounds infected by these bacterial species. PPIX-MED exerted a potent inhibitory effect on the growth of the three bacterial species by producing reactive oxygen species when photoactivated. PPIX-MED-mediated antimicrobial photodynamic therapy (PPIX-MED-aPDT) had high bacterial photoinactivation ability , with a minimum inhibitory concentration of 15.6 μM PPIX-MED against each of the three types of bacteria and minimum bactericidal concentrations of 31.25 μM against MRSA and and 62.5 μM against In rats with third-degree burns infected by a mixture of these bacteria, the bactericidal efficiency of PPIX-MED-aPDT-combined-with-antibiotic treatment was higher than that of antibiotic or aPDT treatment alone. This was confirmed by analysis of viable bacterial counts in wound tissue and blood. Enzyme-linked immunosorbent assay revealed that aPDT-combined-with-antibiotic treatment resulted in an obvious reduction in tumor necrosis factor-alpha and interleukin-6 levels compared with the no-treatment control group and the other treatment groups. Immunohistochemistry revealed that the expression of basic fibroblast growth factor and CD31 (a marker of neovascularization), expressed in burn wound tissue was higher in the aPDT-combined-with-antibiotic treatment group than in the other groups. PPIX-MED-aPDT has a promising bactericidal effect both and , and PPIX-MED-aPDT-combined-with-antibiotic treatment enhanced the healing of infected third-degree burns in rats.

摘要

阳离子卟啉共轭物,原卟啉IX - 甲基乙二胺衍生物(PPIX - MED)对临床分离的细菌,包括耐甲氧西林金黄色葡萄球菌(MRSA)、[此处原文缺失两种细菌名称],具有强大的光敏抗菌作用。本研究调查了(i)PPIX - MED介导的对这三种细菌的抗菌光动力效应,以及(ii)抗菌光动力疗法(aPDT)联合使用抗生素对感染这些细菌的大鼠三度烧伤创面愈合的影响。PPIX - MED在光激活时通过产生活性氧对这三种细菌的生长发挥强大的抑制作用。PPIX - MED介导的抗菌光动力疗法(PPIX - MED - aPDT)具有较高的细菌光灭活能力,对这三种细菌的最小抑菌浓度为15.6 μM PPIX - MED,对MRSA和[此处原文缺失一种细菌名称]的最小杀菌浓度为31.25 μM,对[此处原文缺失一种细菌名称]的最小杀菌浓度为62.5 μM。在感染了这些细菌混合物的三度烧伤大鼠中,PPIX - MED - aPDT联合抗生素治疗的杀菌效率高于单独使用抗生素或aPDT治疗。这通过对伤口组织和血液中活菌计数的分析得到证实。酶联免疫吸附测定显示,与未治疗对照组和其他治疗组相比,aPDT联合抗生素治疗导致肿瘤坏死因子 - α和白细胞介素 - 6水平明显降低。免疫组织化学显示,在烧伤创面组织中表达的碱性成纤维细胞生长因子和CD31(新血管形成的标志物)在aPDT联合抗生素治疗组中的表达高于其他组。PPIX - MED - aPDT在体外和体内均具有有前景的杀菌作用,并且PPIX - MED - aPDT联合抗生素治疗促进了感染的大鼠三度烧伤创面的愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a1/7943878/b0eb27e8bcbe/fmicb-12-622410-g001.jpg

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