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中国防痨杂志 ›› 2025, Vol. 47 ›› Issue (2): 158-163.doi: 10.19982/j.issn.1000-6621.20240315

• 论著 • 上一篇    下一篇

七氟烷对结核分枝杆菌体外抑菌效果的评价

张超1, 于霞1, 黄海荣1, 刘伟2, 刘涛2()   

  1. 1首都医科大学附属北京胸科医院/国家结核病临床实验室,北京 101149
    2首都医科大学附属北京胸科医院麻醉科,北京 101149
  • 收稿日期:2024-07-31 出版日期:2025-02-10 发布日期:2025-02-08
  • 通信作者: 刘涛,Email:mz89509089@sina.com

Evaluation of the in vitro antimicrobial effects of sevoflurane on Mycobacterium tuberculosis

Zhang Chao1, Yu Xia1, Huang Hairong1, Liu Wei2, Liu Tao2()   

  1. 1National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing 101149, China
    2Department of Anesthesiology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
  • Received:2024-07-31 Online:2025-02-10 Published:2025-02-08
  • Contact: Liu Tao, Email: mz89509089@sina.com

摘要:

目的: 探究临床常用镇静、镇痛和肌肉松弛剂对结核分枝杆菌(Mycobacterium tuberculosis,MTB)的体外抑菌活性。方法: 检测5种临床常用镇静剂(包括吸入用的七氟烷和静脉用的丙泊酚)、镇痛剂地佐辛和肌肉松弛剂(罗库溴铵和阿曲库铵)对MTB标准株H37Rv的最低抑菌浓度(minimal inhibit concentration,MIC)。对具有较好体外抑菌活性的七氟烷通过菌落形成单位(CFU)计数方法观察不同浓度处理后MTB的菌落数量变化。制备痰菌悬液模拟痰液环境,观察七氟烷在4h内的抗结核活性;使用人单核细胞白血病细胞(THP-1)验证4h内七氟烷的细胞毒性。结果: 丙泊酚、地佐辛、罗库溴铵和阿曲库铵对MTB均无明显的体外抑菌活性,仅七氟烷在体外对H37Rv有抑菌效果,MIC值为1.25%。进一步发现,3%、6%、9%浓度七氟烷处理8h MTB的菌落计数(log10CFU)分别为3.086±0.196、4.165±0.083和4.162±0.100,均明显低于对照组(4.489±0.083),差异有统计学意义(F=7.630, P=0.003);9%七氟烷处理48h MTB的菌落计数(log10CFU)为3.000±0.000,明显低于对照组的5.077±0.191,差异有统计学意义(F=313.300,P<0.001)。在痰菌悬液中,用9%七氟烷处理2h和4h可产生明显的抗MTB活性,MTB菌落计数(log10CFU)分别为5.846±0.384和5.947±0.280,均明显低于对照组[MTB菌落计数(log10CFU)分别为6.264±0.150和6.331±0.162],差异均有统计学意义(F值分别为4.173和6.091,P值分别为0.025和0.006)。并且CCK-8实验发现,0~9%浓度七氟烷处理THP-1细胞4h内均可维持细胞存活率在(81.033±3.190)%以上。结论: 七氟烷具有良好的体外抗MTB活性,在模拟痰液环境中保持短时间杀菌的效果,且安全性良好。

关键词: 分枝杆菌,结核, 微生物敏感性试验, 催眠药和镇静药, 体外研究, 七氟烷

Abstract:

Objective: To investigate the in vitro antimicrobial activities of commonly used sedatives, analgesics, and muscle relaxants against Mycobacterium tuberculosis (MTB). Methods: The minimum inhibitory concentrations (MICs) of five clinically common sedatives, including sevoflurane and propofol, the analgesic dezocine, and the muscle relaxants rocuronium and atracurium, were determined against the standard MTB strain H37Rv. Colony-forming unit (CFU) counting was employed to evaluate the changes in MTB colony numbers following treatment with varying concentrations of sevoflurane, which demonstrated notable antimicrobial activity in vitro. A sputum-bacterial suspension was prepared to simulate the sputum environment, and the anti-tuberculosis activity of sevoflurane was evaluated over a 4-hour period. Additionally, the cytotoxicity of sevoflurane within 4 hours was assessed using the THP-1 cell line. Results: Propofol, dexmedetomidine, rocuronium bromide, and atracurium demonstrated no significant in vitro antibacterial activity against MTB. In contrast, sevoflurane exhibited potent antibacterial activity against H37Rv in vitro, with a MIC value of 1.25%. Further analysis showed that treatment with sevoflurane at concentrations of 3%, 6%, and 9% for 8 hours reduced MTB colony counts (log10CFU) to 3.086±0.196, 4.165±0.083, and 4.162±0.100, respectively. These values were significantly lower than those of the control group (4.489±0.083), with statistical significance (F=7.630, P=0.003). The colony count (log10CFU) of MTB treated with 9% sevoflurane for 48 hours was 3.000±0.000, significantly lower than that of the control group (5.077±0.191), with a statistically significant difference (F=313.300, P<0.001). In sputum suspension, treatment with 9% sevoflurane for 2 and 4 hours demonstrated significant anti-MTB activity, reducing MTB colony counts (log10CFU) to 5.846±0.384 and 5.947±0.280, respectively. These values were significantly lower than those in the control group (log10CFU: 6.264±0.150 and 6.331±0.162, respectively), with statistically significant differences (F=4.173, P=0.025; F=6.091, P=0.006). Furthermore, CCK-8 experiments indicated that treatment with sevoflurane at concentrations ranging from 0% to 9% maintained a cell survival rate of ≥(81.033±3.190) % in THP-1 cells over 4 hours. Conclusion: Sevoflurane exhibits strong anti-MTB activity in vitro, demonstrating short-term bacteriostatic effects under simulated conditions and maintaining favorable safety profiles.

Key words: Mycobacterium tuberculosis, Antimicrobial susceptibility tests, Hypnotics and sedatives, In vitro study, Sevoflurane

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