SHAO Zhongxin, LI Shiying. Effect of propofol regulating macrophage polarization on airway inflammatory response and Toll-like receptor 4-NOD-like receptor protein 3 pathway in mice with bronchial asthma[J]. Journal of Clinical Medicine in Practice, 2025, 29(6): 13-19. DOI: 10.7619/jcmp.20245587
Citation: SHAO Zhongxin, LI Shiying. Effect of propofol regulating macrophage polarization on airway inflammatory response and Toll-like receptor 4-NOD-like receptor protein 3 pathway in mice with bronchial asthma[J]. Journal of Clinical Medicine in Practice, 2025, 29(6): 13-19. DOI: 10.7619/jcmp.20245587

Effect of propofol regulating macrophage polarization on airway inflammatory response and Toll-like receptor 4-NOD-like receptor protein 3 pathway in mice with bronchial asthma

More Information
  • Received Date: November 14, 2024
  • Revised Date: January 12, 2025
  • Objective 

    To investigate the effect of propofol (Pro) regulating macrophage polarization on airway inflammatory response and Toll-like receptor 4-NOD-like receptor protein 3 (TLR4-NLRP3) pathway in mice with bronchial asthma (BA).

    Methods 

    Forty BA model mice were randomly divided into BA group, low-dose Pro (Pro-L) group, high-dose Pro (Pro-H) group, and Pro-H+lipopolysaccharide (LPS) group, with 10 mice in each group. Additionally, 10 normal mice were included as control group. Lung function indicators[peak expiratory flow (PEF) and ventilation volume (VE)], eosinophil (EOS), lymphocyte (LYM) and neutrophil (NEU) counts in bronchoalveolar lavage fluid, and interleukin (IL)-4, IL-10, IL-5 and IL-13 levels were measured in each group; flow cytometry was used to detect M1 and M2 macrophage levels and the proportions of T helper (Th) 1 and Th2 cells in peripheral blood; the enzyme-linked immunosorbent assay (ELISA) was used to detect serum interferon-γ (IFN-γ) and immunoglobulin E (IgE) levels; the hematoxylin-eosin (HE) staining was used to observe the pathological morphology of lung tissues; the Western blot was used to detect the protein expression of cleaved caspase-3, TLR4, NLRP3 and Caspase-1 in lung tissues.

    Results 

    Compared with the control group, mice in the BA group showed significant lung tissue damage, decreased PEF, VE, IL-10 and M1 macrophage levels, Th1 cell proportion, and IFN-γ level, and significant increased EOS, LYM, NEU counts, IL-4, IL-5, IL-13 and M2 macrophage levels, Th2 cell proportion, IgE, cleaved caspase-3, TLR4, NLRP3, and Caspase-1 protein expression levels (P < 0.05). Compared with the BA group, mice in the Pro-L and Pro-H groups showed significant lung tissue damage, increased PEF, VE, IL-10 and M1 macrophage levels, Th1 cell proportion, and IFN-γ level, and significant decreased EOS, LYM, NEU counts, IL-4, IL-5, IL-13 and M2 macrophage levels, Th2 cell proportion, IgE, cleaved caspase-3, TLR4, NLRP3, and Caspase-1 protein expression levels (P < 0.05). LPS significantly attenuated the improvement effect of Pro in BA mice (P < 0.05).

    Conclusion 

    Pro may regulate macrophage polarization and immune response in BA mice by inhibiting the TLR4-NLRP3 signaling pathway, reducing the degree of inflammatory response, and improving lung tissue morphology and lung function.

  • [1]
    YIN H, FAN Y, MU D, et al. Transcriptomic analysis exploring the molecular mechanisms of hanchuan zupa granules in alleviating asthma in rat[J]. Evid Based Complement Alternat Med, 2021, 2021(4): 5584099-5584109.
    [2]
    PAN L Y, GONG C X, CHEN Y, et al. Yanghe Pingchuan granules mitigates oxidative stress and inflammation in a bronchial asthma rat model: role of the IKK/IκB/NF-κB signalling pathway[J]. Ann Med Surg (Lond), 2023, 86(1): 212-218.
    [3]
    XIE M, LIU T, YIN J, et al. Kechuanning gel plaster exerts anti-inflammatory and immunomodulatory effects on ovalbumin-induced asthma model rats via ERK pathway[J]. Comb Chem High Throughput Screen, 2024, 27(1): 69-77.
    [4]
    ZHANG R Z, ZHAI K R, HUANG J, et al. Sevoflurane alleviates lung injury and inflammatory response compared with propofol in a rat model of VV ECMO[J]. Perfusion, 2024, 39(1): 142-150.
    [5]
    李泓邑. 丙泊酚通过调节TLR4/ROS/NF-κB信号通路抑制肥大细胞依赖型哮喘小鼠气道炎症的研究[D]. 北京: 北京协和医学院, 2018.
    [6]
    王姝晨. 基于Nrf2信号通路探讨丙泊酚调控哮喘小鼠气道炎症的机制研究[D]. 广州: 广州中医药大学, 2023.
    [7]
    LYU M, QIN J, HUANG S, et al. Tuo-Min-Ding-Chuan decoction alleviates airway inflammations in the allergic asthmatic mice model by regulating tlr4-nlrp3 pathway mediated pyroptosis: a network pharmacology and experimental verification study[J]. Drug Des Devel Ther, 2023, 17(2): 1613-1630.
    [8]
    费园园, 葛明坤, 卞庆平. 基于Notch信号通路探讨牡荆素对哮喘模型小鼠的改善作用[J]. 中国药房, 2024, 35(15): 1849-1854.
    [9]
    缪文禹, 毛舜, 佟昌慈. 丙泊酚通过激活Nrf2/HO-1信号通路减轻脓毒症诱导的急性肺损伤[J]. 解剖科学进展, 2024, 30(1): 29-31, 35.
    [10]
    范慧慧, 任玉梅, 田新磊, 等. 止咳平喘方对支气管哮喘小鼠气道炎症及TLR4/TRAF6/NF-κB通路的影响[J]. 天津医药, 2024, 52(9): 924-929.
    [11]
    WANG J R, GAO S N, ZHANG J Y, et al. Interleukin-22 attenuates allergic airway inflammation in ovalbumin-induced asthma mouse model[J]. BMC Pulm Med, 2021, 21(1): 385. doi: 10.1186/s12890-021-01698-x
    [12]
    WANG W, XU L, ZHOU L, et al. Dioscorea nipponica makino relieves ovalbumin-induced asthma in mice through regulating RKIP-mediated Raf-1/MEK/MAPK/ERK Signaling Pathway[J]. Biomed Res Int, 2022, 2022(1): 8077058-8077069.
    [13]
    肖鉴峰. 支气管哮喘患者BALF中T淋巴细细胞、TGF-β1及IL-6的水平变化及意义[J]. 检验医学与临床, 2023, 20(21): 3144-3147, 3151.
    [14]
    王立琼, 黄娟, 张芳霞, 等. 黄芩总黄酮对支气管哮喘大鼠的治疗作用及miR133a-3-p/NOX4/NLRP3信号轴表达的影响[J]. 检验医学与临床, 2024, 21(10): 1436-1442.
    [15]
    TEE J H, VIJAYAKUMAR U, SHANMUGASUNDARAM M, et al. Isthmin-1 attenuates allergic Asthma by stimulating adiponectin expression and alveolar macrophage efferocytosis in mice[J]. Respir Res, 2023, 24(1): 269.
    [16]
    王从瑶, 田春燕, 李竹英. 度普利尤单抗在中重度支气管哮喘治疗中的研究进展[J]. 中华全科医学, 2024, 22(9): 1571-1575.
    [17]
    王亚南, 戴倩倩, 茹凉. 支气管哮喘患儿血清Rac1水平变化及临床意义[J]. 中华全科医学, 2023, 21(5): 736-739.
    [18]
    YU H, CHEN L, YUE C J, et al. Effects of propofol and sevoflurane on T-cell immune function and Th cell differentiation in children with SMPP undergoing fibreoptic bronchoscopy[J]. Ann Med, 2022, 54(1): 2574-2580.
    [19]
    孟景霞. 丙泊酚通过GABAA受体抑制Th2型哮喘炎症相关机制的研究[D]. 北京: 北京协和医学院, 2018.
    [20]
    WANG K, CAO X M, YANG L, et al. Modulating Th1/Th2 drift in asthma-related immune inflammation by enhancing bone mesenchymal stem cell homing through targeted inhibition of the Notch1/Jagged1 signaling pathway[J]. Int Immunopharmacol, 2024, 130: 111713.
    [21]
    杨霞, 宁宗. 巨噬细胞极化调控信号通路及M1/M2失衡在肺部炎症性疾病中作用的研究进展[J]. 山东医药, 2023, 63(26): 88-91.
    [22]
    YU H, HUANG X, XIE C, et al. Transcriptomics reveals apigenin alleviates airway inflammation and epithelial cell apoptosis in allergic asthma via MAPK pathway[J]. Phytother Res, 2023, 37(9): 4002-4017.
    [23]
    齐莎莎, 吕民英, 付晓梅, 等. 鹰嘴豆芽素A通过调节TLR4/NF-κB/NLRP3信号通路减轻卵清蛋白诱导哮喘大鼠的气道炎症[J]. 天津中医药, 2023, 40(4): 506-512.
    [24]
    LIU L, ZHOU L, WANG L L, et al. MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway[J]. Respir Res, 2023, 24(1): 255.

Catalog

    Article views (34) PDF downloads (4) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return