蓝萼甲素调控TLR4/NF-κB通路对脓肿分枝杆菌生长及生物膜形成的影响

doi:10.3969/j.issn.1006-6233.2025.02.006

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摘要 目的: 探讨蓝萼甲素调控Toll样受体4(TLR4)/核转录因子-κB(NF-κB)通路对脓肿分枝杆菌生长及生物膜形成的影响。方法: 脓肿分枝杆菌菌株ATCC19977分为空白组、低剂量蓝萼甲素组、中剂量蓝萼甲素组、高剂量蓝萼甲素组、TAK-242组、高剂量蓝萼甲素+LPS组,阿尔玛蓝液体药敏法测定蓝萼甲素对ATCC19977的抑制率大于等于90%对应的最低药物浓度(MIC₉₀);扫描电镜观察ATCC19977生物膜形成;结晶紫染色检测ATCC19977生物膜总生物量;MTT检测ATCC19977生物膜代谢活性;qRT-PCR检测ATCC19977中MAB_2030、MAB_2028 mRNA表达;Western blot检测ATCC19977中TLR4、p-NF-κB p65蛋白。结果: 蓝萼甲素对ATCC19977的MIC₉₀为10μmoL/L。与空白组比较,低剂量蓝萼甲素组、中剂量蓝萼甲素组、高剂量蓝萼甲素组ATCC19977数量减少,生物膜被破坏,表现为厚度变薄,且呈松散状态,ATCC19977生物膜总生物量、生物膜代谢活性、ATCC19977中MAB_2030、MAB_2028 mRNA表达及TLR4、p-NF-κB p65蛋白表达降低,且高剂量蓝萼甲素组趋势最明显,TAK-242组对应指标变化趋势与上述一致(P<0.05);与高剂量蓝萼甲素组比较,高剂量蓝萼甲素+LPS组ATCC19977数量增多,生物膜破坏程度有所减弱,ATCC19977生物膜总生物量、生物膜代谢活性、ATCC19977中MAB_2030、MAB_2028 mRNA表达及TLR4、p-NF-κB p65蛋白表达升高(P<0.05)。结论: 蓝萼甲素可能通过抑制TLR4/NF-κB通路抑制ATCC19977生长及生物膜形成。

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关键词 ：蓝萼甲素, 脓肿分枝杆菌, 生物膜, Toll样受体4/核转录因子-κB通路

Abstract：Objective: To investigate the effects of glaucocalyxin A (GLA) on on the growth and biofilm formation of Mycobacterium abscessus via regulating toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Mycobacterium abscessus strain ATCC19977 was inducted into blank group, GLA low, medium high-dose group, TAK-242 group and GLA high-dose group + LPS group. The lowest drug concentration (MIC90) corresponding to an inhibition rate of 90% or greater on ATCC19977 by GLA determined by Alma Blue liquid drug sensitivity assay. The biofilm formation in ATCC19977 was recorded by scanning electron microscopy. Crystal violet staining was employed to detect the total biomass of ATCC19977 biofilm, MTT assay was used to detect the metabolic activity of ATCC19977 biofilm. The quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA expression of MAB-2030 and MAB-2028 and the proteins expression of TLR4 and p-NF-κB p65 in ATCC19977. Results: The MIC90 of GLA on ATCC19977 was 10μmoL/L. Compared with the blank group, the GLA dose groups showed a decrease in the number of ATCC19977, and the biofilm formation was damaged, manifested as a thinner thickness and a loose state. The total biomass and metabolic activity of ATCC19977 biofilm, mRNA expression of MAB-2030 and MAB-2028, protein expression of TLR4 and p-NF -κB p65 in ATCC19977 of the GLA dose groups decreased significantly, and the GLA high-dose group showed the most obvious trend, the corresponding indicator change trend in TAK-242 group was consistent with the above (all P<0.05). Compared with the GLA high-dose group, the GLA high-dose+LPS group had an increase in the number of ATCC19977, a decrease in the degree of biofilm damage, increases in total biofilm biomass, biofilm metabolic activity, MAB-2030 and MAB-2028 mRNA expression, and TLR4 and p-NF -κB p65 protein expression in ATCC19977 (all P<0.05). Conclusion: GLA may inhibit the growth and biofilm formation of ATCC19977 by suppressing the TLR4/NF -κB signaling pathway.

Key words： Glaucocalyxin A Mycobacterium abscessus Biofilm Toll like receptor 4/nuclear factor -κB signaling pathway

基金资助:河北省2023年度医学科学研究课题,(编号:20231230)

通讯作者: 李曼

引用本文:

李倩, 任哲, 杨丙宙, 杨娜, 李曼. 蓝萼甲素调控TLR4/NF-κB通路对脓肿分枝杆菌生长及生物膜形成的影响[J]. 河北医学, 2025, 31(2): 209-215.
LI Qian, REN Zhe, YANG Bingzhou, et al. Effect of Glaucocalyxin A on Growth and Biofilm Formation of Mycobacterium Abscessus via Regulating TLR4/NF-κB Signaling Pathway. HeBei Med, 2025, 31(2): 209-215.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.02.006 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I2/209

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