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

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 indicatorspeak 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.