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抗菌肽BMAP-28可降低葡萄球菌败血症小鼠模型的致死率。

The antimicrobial peptide BMAP-28 reduces lethality in mouse models of staphylococcal sepsis.

作者信息

Giacometti Andrea, Cirioni Oscar, Ghiselli Roberto, Bergnach Cristina, Orlando Fiorenza, D'Amato Giuseppina, Mocchegiani Federico, Silvestri Carmela, Del Prete Maria Simona, Skerlavaj Barbara, Saba Vittorio, Zanetti Margherita, Scalise Giorgio

机构信息

Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.

出版信息

Crit Care Med. 2004 Dec;32(12):2485-90. doi: 10.1097/01.ccm.0000148221.09704.22.

DOI:10.1097/01.ccm.0000148221.09704.22
PMID:15599155
Abstract

OBJECTIVE

A mouse model of staphylococcal sepsis was used to compare the efficacy of the bovine antimicrobial peptide BMAP-28, a compound of the cathelicidin family, with that of conventional antibiotics.

DESIGN

Prospective, randomized, controlled animal study.

SETTING

Research laboratory in a university hospital.

SUBJECTS

BALB/c male mice.

INTERVENTIONS

BALB/c mice were injected intravenously with 2.0 x 10(6) colony-forming units of live Staphylococcus aureus ATCC 25923 or with 5.0 x 10(8) heat-killed cells of the same strain. All animals were randomized to receive intravenously isotonic sodium chloride solution, 2 mg/kg BMAP-28, 7 mg/kg imipenem, 7 mg/kg vancomycin, 7 mg/kg clindamycin, and 7 mg/kg clarithromycin immediately and at 6 hrs after bacterial challenge.

MEASUREMENTS AND MAIN RESULTS

Lethality, quantitative blood cultures, and detection of tumor necrosis factor-alpha and interleukin-6 plasma levels. In the experiments performed with live bacteria, all compounds reduced lethality rates and bacterial growth compared with controls. Imipenem and vancomycin exhibited the highest efficacy on these main outcome measures. In the experiments performed using heat-killed organisms, only BMAP-28 demonstrated significant efficacy on lethality rates, tumor necrosis factor-alpha, and interleukin-6 plasma levels compared with controls.

CONCLUSION

These results highlight the capacity of BMAP-28 to reduce the effects of components of the bacterial cells and suggest that it may be beneficial in the treatment of severe staphylococcal infections in concert with other antimicrobial agents.

摘要

目的

使用葡萄球菌败血症小鼠模型比较牛抗菌肽BMAP - 28(一种cathelicidin家族化合物)与传统抗生素的疗效。

设计

前瞻性、随机、对照动物研究。

地点

大学医院的研究实验室。

对象

BALB/c雄性小鼠。

干预措施

给BALB/c小鼠静脉注射2.0×10⁶个活的金黄色葡萄球菌ATCC 25923菌落形成单位或5.0×10⁸个同一菌株的热灭活细胞。所有动物随机分组,在细菌攻击后立即及6小时后静脉注射等渗氯化钠溶液、2mg/kg BMAP - 28、7mg/kg亚胺培南、7mg/kg万古霉素、7mg/kg克林霉素和7mg/kg克拉霉素。

测量指标及主要结果

死亡率、定量血培养以及肿瘤坏死因子 - α和白细胞介素 - 6血浆水平的检测。在用活细菌进行的实验中,与对照组相比,所有化合物均降低了死亡率和细菌生长。亚胺培南和万古霉素在这些主要结局指标上显示出最高疗效。在用热灭活生物体进行的实验中,与对照组相比,仅BMAP - 28在死亡率、肿瘤坏死因子 - α和白细胞介素 - 6血浆水平方面显示出显著疗效。

结论

这些结果突出了BMAP - 28减轻细菌细胞成分影响的能力,并表明它与其他抗菌剂协同治疗严重葡萄球菌感染可能有益。

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