甘草查尔酮A与三种抗生素联用对产气荚膜梭菌感染小鼠的治疗作用

doi:10.11843/j.issn.0366-6964.2024.01.031

畜牧兽医学报 ›› 2024, Vol. 55 ›› Issue (1): 334-345.doi: 10.11843/j.issn.0366-6964.2024.01.031

甘草查尔酮A与三种抗生素联用对产气荚膜梭菌感染小鼠的治疗作用

周文惠¹, 包红霞¹, 王俊豪¹, 黄远玲¹, 王文惠¹, 郝海红^1,2,3,4,5*

1. 华中农业大学, 农业微生物资源发掘与利用全国重点实验室, 武汉 430070;
2. 动物育种与健康养殖前沿科学中心, 武汉 430070;
3. 华中农业大学, 农业农村部畜禽产品质量安全风险评估实验室, 武汉 430070;
4. 华中农业大学-深圳营养与健康研究院, 深圳 518000;
5. 石河子大学动物科技学院, 石河子 832000

收稿日期:2023-03-13 出版日期:2024-01-23 发布日期:2024-01-24
通讯作者: 郝海红,主要从事细菌耐药性研究,E-mail:haihong_hao@aliyun.com
作者简介:周文惠(2001-),女,山东潍坊人,本科生,主要从事细菌耐药性研究,E-mail:993923400@qq.com
基金资助:
国家重点研发计划（2022YFA1304104；2021YFD1800600）；国家自然科学基金（32172914）；中央高校自主创新基金（2662022DKYJC005）；湖北省自然科学基金（2021CFA016）；现代农业产业技术体系项目（CARS-41）

Therapeutic Effect of Licorice Chalcone A in Combination with Three Antibiotics on Clostridium perfringens Infection in Mice

ZHOU Wenhui¹, BAO Hongxia¹, WANG Junhao¹, HUANG Yuanling¹, WANG Wenhui¹, HAO Haihong^1,2,3,4,5*

1. State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China;
2. Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China;
3. MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China;
4. Huazhong Agricultural University, Shenzhen Institute of Nutrition and Health, Shenzhen 518000, China;
5. College of Animal Science and Technology, Shihezi University, Shihezi 832000, China

Received:2023-03-13 Online:2024-01-23 Published:2024-01-24

摘要/Abstract

摘要： 本研究旨在研究中药单体与抗生素联用对产气荚膜梭菌（Clostridium perfringens，CP）感染小鼠的影响。本试验以甘草查尔酮A（licorice chalcone A， LCA）为代表药物，探究LCA与抗生素联用的体外和体内治疗效果，通过联合药敏试验确定与中药单体LCA有协同作用的抗生素，测定了产气荚膜梭菌在不同浓度药物作用下的杀菌曲线、溶血试验、滑动试验以及对小鼠的气性坏疽治疗效果，比较不同种抗生素在不同浓度下与LCA联用的治疗作用。结果表明，克林霉素（clindamycin，CLDM）、四环素（tetracycline，TCN）、替米考星（tilmicosin，TMS）三种抗生素与LCA有协同作用。根据杀菌曲线结果显示，8 μg·mL^-1 LCA和16 μg·mL^-1TMS几乎可以完全杀灭产气荚膜梭菌；2 μg·mL^-1 LCA与2 μg·mL^-1 TMS 联合使用可显著降低细菌的溶血性，溶血几乎完全被抑制（溶血定量为9.08%）。值得注意的是，LCA对细菌的迁移力有一定的促进作用，能够提高菌毛介导的运动性，与TMS联用后其促进作用显著提升。动物体内试验结果表明，CLDM单独使用时对产气荚膜梭菌具有较好的抑制作用，治疗效果显著；TCN和TMS分别与LCA联合使用时表现出协同作用（FIC指数为0.375），同时治疗时也表现出较好的增效效果。因此，在治疗产气荚膜梭菌感染时，TMS与LCA联合作用，可以降低药物使用量并提高治疗效果。

关键词: 甘草查尔酮A, 产气荚膜梭菌, 气性坏疽, 替米考星, 四环素, 克林霉素

Abstract: The aim of this study was to investigate the effect of Chinese herbal monomers in combination with antibiotics on Clostridium perfringens (CP) infection in mice. In this study, licorice chalcone A (LCA) was used as a representative drug to investigate the in vitro and in vivo therapeutic effects of LCA in combination with antibiotics. Some antibiotics were identified by combined drug sensitivity tests as having synergistic effects with the monomeric LCA of Chinese medicine. The therapeutic effect of the three antibiotics in combination with LCA at different concentrations was compared by measuring the bactericidal profile of Clostridium perfringens at different concentrations, the hemolysis test, the sliding test and therapeutic effect on gas gangrene in mice. Three antibiotics, clindamycin (CLDM), tetracycline (TCN), and tilmicosin (TMS), which have synergistic effects with the LCA, were identified by combined drug sensitivity tests for follow-up trials. According to the bactericidal curve results, LCA at 8 μg·mL^-1 and TMS at 16 μg·mL^-1 can almost completely kill Clostridium perfringens. The combination of LCA and TMS (both 2 μg·mL^-1) significantly reduced bacterial hemolysis and hemolysis was almost completely inhibited (hemolysis quantified at 9.08%). It is worth noting that LCA has a facilitating effect on bacterial mobility and can improve hair-mediated motility, and its facilitating effect is significantly enhanced when combined with TMS. The results of the animal studies showed that CLDM alone had a good inhibitory effect on Clostridium perfringens and was clinically effective; TCN and TMS each showed a synergistic effect (FIC index of 0.375) when combined with LCA, and also showed a good synergistic effect in treatment. In practice, therefore, TMS can be used in combination with LCA in the treatment of Clostridium perfringens infections to reduce the amount of medication used while improving the therapeutic effect.

Key words: licorice chalcone A, Clostridium perfringens, gas gangrene, tilmicosin, tetracycline, clindamycin

中图分类号:

S859.7

周文惠, 包红霞, 王俊豪, 黄远玲, 王文惠, 郝海红. 甘草查尔酮A与三种抗生素联用对产气荚膜梭菌感染小鼠的治疗作用[J]. 畜牧兽医学报, 2024, 55(1): 334-345.

ZHOU Wenhui, BAO Hongxia, WANG Junhao, HUANG Yuanling, WANG Wenhui, HAO Haihong. Therapeutic Effect of Licorice Chalcone A in Combination with Three Antibiotics on Clostridium perfringens Infection in Mice[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(1): 334-345.

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甘草查尔酮A与三种抗生素联用对产气荚膜梭菌感染小鼠的治疗作用

Therapeutic Effect of Licorice Chalcone A in Combination with Three Antibiotics on Clostridium perfringens Infection in Mice

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