中华皮肤科杂志 ›› 2026, Vol. 59 ›› Issue (1): 44-50.doi: 10.35541/cjd.20240630

• 论著 • 上一篇    下一篇

低温等离子体治疗小鼠非开放性金黄色葡萄球菌感染性皮肤病的有效性和安全性评价

王溯1    吴晋彤1，2    李文钰3    章程4    李承新1    王睿1   

  1. 1解放军总医院第一医学中心皮肤科，北京  100853；2解放军医学院，北京  100853；3北京大学第三医院北方院区，北京  100089；4中国科学院电工研究所，北京  100190
  • 收稿日期:2024-11-18 修回日期:2025-08-19 发布日期:2026-01-06
  • 通讯作者: 王睿 E-mail:wr0699@163.com
  • 基金资助:
    国家自然科学基金（82273530）

Efficacy and safety of cold atmospheric plasma in the treatment of non-open Staphylococcus aureus skin infections in mice

Wang Su1, Wu Jintong1,2, Li Wenyu3, Zhang Cheng4, Li Chengxin1, Wang Rui1   

  1. 1Department of Dermatology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; 2Chinese PLA Medical School, Beijing 100853, China; 3Northern Section of Peking University Third Hospital, Beijing 100089, China; 4Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190, China
  • Received:2024-11-18 Revised:2025-08-19 Published:2026-01-06
  • Contact: Wang Rui E-mail:wr0699@163.com
  • Supported by:
    National Natural Science Foundation of China（82273530）

PDF

0

摘要： 【摘要】 目的 探讨低温等离子体（CAP）治疗小鼠非开放性金黄色葡萄球菌（简称金葡菌）感染性皮肤病的有效性和安全性。方法 将金葡菌悬液均匀涂布于12块血平板中，随机分为4组，每组3块，未接受CAP照射的一组作为对照组，另3组分别用3档、5档、8档CAP照射血平板3 min，培养24 h后进行菌落计数。予30只无特定病原体（SPF）级BALB/c小鼠皮下注射金葡菌悬液0.05 ml，24 h后肉眼可见皮下脓肿形成，即皮下脓肿模型构建成功。根据脓肿体积采用分层随机法，将30只皮下脓肿模型小鼠分为3组：对照组不予任何处理，莫匹罗星组小鼠背部涂抹莫匹罗星软膏，CAP组接受CAP照射，每天1次，共10 d，隔天观察小鼠的脓肿体积及外观变化，并在干预结束后进行病原学及病理学检查，1只未经任何干预的正常小鼠背部皮肤病理表现作为对照。12只SPF级BALB/c小鼠随机分为4组，以8档CAP强度按照不同时间、不同距离照射小鼠背部皮肤，记录小鼠背部皮肤红斑、水肿等情况并进行评分。体外抗菌有效性分析采用Kruskal-Wallis H检验；体内实验中，小鼠脓肿体积变化行重复测量方差分析，脓肿菌量行单因素方差分析；安全性分析采用双因素方差分析。结果 CAP对金葡菌的体外抗菌有效性评价结果显示，4组间存活菌量差异有统计学意义（H = 10.42，P = 0.015），8档CAP组存活菌量［M（Q1，Q3）为20（0，40）CFU/ml］低于对照组［560（400， 600）CFU/ml］（P = 0.013），其余组间差异无统计学意义（均P > 0.05）。造模成功后，对照组、莫匹罗星组及CAP组小鼠初始脓肿体积差异无统计学意义（F = 0.14，P = 0.865）。3组小鼠脓肿体积均呈早期增大、后期减小的趋势，脓肿体积随时间的变化有统计学意义（F = 426.50，P < 0.001，偏η2 = 0.94），不同组间脓肿体积整体差异有统计学意义（F = 1.62，P = 0.020，偏η2 = 0.25），但3组脓肿体积变化趋势不同（F = 2.69，P = 0.031，偏η2 = 0.17）；干预第6、8、10天，CAP组的脓肿体积低于对照组（均P < 0.05）；干预第8、10天，莫匹罗星组低于对照组（均P < 0.05）；干预期间，CAP组与莫匹罗星组间脓肿体积差异均无统计学意义（均P＞0.05）。干预10 d后，莫匹罗星组［x ± s为（4.16 ± 0.18） lg CFU/ml］及CAP组［（3.75 ± 0.27） lg CFU/ml］脓肿菌量均低于对照组［（4.98 ± 0.32） lg CFU/ml］（均P < 0.001），且CAP组低于莫匹罗星组（P = 0.029）。干预10 d后，小鼠皮肤病理检查显示，与正常小鼠皮肤相比，对照组、莫匹罗星组、CAP组皮下均可见明显的脓肿灶，灶内有大量中性粒细胞浸润，CAP组及莫匹罗星组的浸润程度低于对照组。8档CAP，距离0.5 cm照射5 min及10 min后均较安全，小鼠背部皮肤无明显刺激反应；8档CAP，距离0 cm照射5 min及10 min后，小鼠背部均可出现红斑、水肿反应，且刺激反应随着照射时间的延长而加重，24 h后上述不良反应均消退。结论 CAP治疗非开放性金葡菌感染性皮肤病安全且有效，有望成为治疗非开放性细菌性皮肤病的新兴疗法。

关键词: 皮肤疾病, 细菌性, 脓肿, 低温等离子体, 治疗, 有效性, 安全性

Abstract: 【Abstract】 Objective To evaluate the efficacy and safety of cold atmospheric plasma （CAP） in the treatment of non-open Staphylococcus aureus skin infections in mice. Methods In the in vitro antibacterial efficacy experiment, Staphylococcus aureus suspension was evenly inoculated onto 12 blood agar plates, which were randomly divided into 4 groups （3 plates in each group）: the group receiving no CAP irradiation served as the control group, and the other 3 groups were irradiated with CAP at intensity levels 3, 5, and 8 for 3 minutes. Colony counts were calculated after 24 hours of incubation. In the in vivo efficacy experiment, a subcutaneous abscess model was established in 30 specific pathogen-free （SPF） BALB/c mice by subcutaneous injection of 0.05 ml of a Staphylococcus aureus suspension, and successful modeling was confirmed 24 hours later by visible abscess formation. According to the abscess volume, 30 mouse models of subcutaneous abscesses were divided into 3 groups using a stratified randomization method （10 mice in each group）: a control group （without intervention）, a mupirocin group （treated with topical mupirocin ointment on the mouse back）, and a CAP group （treated with CAP irradiation）. Interventions were given once daily for 10 days. Abscess volume and appearance were observed every other day. Microbiological and histopathological examinations were performed after the end of treatment, with skin tissues from one untreated normal mouse serving as the histopathological control. In the safety assessment experiment, 12 SPF BALB/c mice were randomly divided into 4 groups to be irradiated with CAP at intensity level 8 for varying durations and distances. Skin reactions （such as erythema and edema） were recorded and scored. The Kruskal-Wallis H test was used for in vitro antibacterial efficacy analysis; in the in vivo experiment, changes in abscess volume were analyzed by repeated-measures analysis of variance, and bacterial loads in abscesses were compared using one-way analysis of variance; two-way analysis of variance was used in the safety analysis. Results In the in vitro antibacterial efficacy experiment, a significant difference in viable colony counts was observed among the 4 groups （H = 10.42, P = 0.015）, the level 8 CAP group showed significantly decreased viable colony counts （median ［Q1, Q3］: 20 ［0, 40］ colony-forming units ［CFU］/ml） compared with the control group （560 ［400, 600］ CFU/ml, P = 0.013）, while there were no significant differences in viable colony counts between the other groups （all P > 0.05）. After successful modeling, no significant difference in the initial abscess volume was found among the control group, mupirocin group, and CAP group （F = 0.14, P = 0.865）. The abscess volume in all groups showed an initial increase followed by a decrease over time, with a significant main effect of time （F = 426.50, P < 0.001, partial η2 = 0.94）, a significant main effect of treatment （F = 1.62, P = 0.020, partial η2 = 0.25）, and a significant time-treatment interaction effect （F = 2.69, P = 0.031, partial η2 = 0.17）; on days 6, 8, and 10, the abscess volume was significantly lower in the CAP group than in the control group （all P < 0.05）; on days 8 and 10, the abscess volume was significantly lower in the mupirocin group than in the control group （both P < 0.05）; there were no significant differences in the abscess volume between the CAP group and the mupirocin group at any of the aforementioned time points （all P > 0.05）. After 10 days, bacterial loads in abscesses were significantly lower in both the mupirocin group （［4.16 ± 0.18］ lg CFU/ml） and the CAP group （［3.75 ± 0.27］ lg CFU/ml） than in the control group （［4.98 ± 0.32］ lg CFU/ml, both P < 0.001）, and significantly lower in the CAP group than in the mupirocin group （P = 0.029）. After 10 days, histopathological examination showed obvious subcutaneous abscesses with massive neutrophil infiltration in the control group, mupirocin group, and CAP group compared with the histopathological control group （normal mouse skin tissues）, and the degree of infiltration was lower in the CAP group and mupirocin group than in the control group. In the safety analysis, CAP irradiation at level 8 and a distance of 0.5 cm for 5 or 10 minutes was found to be relatively safe, without marked skin irritation on the mouse dorsal skin; CAP irradiation at level 8 and a distance of 0 cm for 5 or 10 minutes could induce erythema and edema, and the irritant reactions worsened with the extension of exposure duration. All adverse reactions subsided within 24 hours. Conclusion CAP was safe and effective for the treatment of non-open Staphylococcus aureus skin infections in mice, suggesting its potential as an emerging therapy for non-open bacterial skin infections.

Key words: Skin diseases, bacterial, Abscess, Cold atmospheric plasma, Treatment, Efficacy, Safety

引用本文

王溯 吴晋彤 李文钰 章程 李承新 王睿. 低温等离子体治疗小鼠非开放性金黄色葡萄球菌感染性皮肤病的有效性和安全性评价[J]. 中华皮肤科杂志, 2026,59(1):44-50. doi:10.35541/cjd.20240630

Wang Su, Wu Jintong, Li Wenyu, Zhang Cheng, Li Chengxin, Wang Rui. Efficacy and safety of cold atmospheric plasma in the treatment of non-open Staphylococcus aureus skin infections in mice[J]. Chinese Journal of Dermatology, 2026, 59(1): 44-50.doi:10.35541/cjd.20240630