[Study on the active components of Xanthium sibiricum promoting the repair of nasal mucosal barrier in allergic rhinitis rats through autophagy-metabolic reprogramming].

Objective To investigate the effect of active components of Xanthii Fructus (XF) on the repair of nasal mucosal barrier in allergic rhinitis (AR) rats through autophagy-metabolic reprogramming. Methods 24 female Sprague-Dawley rats (SD; 5 weeks old) were randomly divided into control group, AR group and XF group, with 8 rats in each group. an AR rat model induced by ovalbumin (OVA) was established. The behavioral changes of rats were observed, and Western blot analysis revealed the expression levels of the NOD-like receptor family contained pyrin domain 3 (NLRP3), mitochondrial outer membrane protein transposase 20 (TOM20), microtubule-associated protein 1 light chain 3B(LC3B), selective autophagy linker 1(P62), PTEN-induced putative kinase 1 (PINK1), Parkin (Parkin), interleukin 1β(IL-1β) and IL-18. Human nasal epithelial cell lines (HNEpCs) were divided into the following groups: blank group (Con), IL-13 group, IL-13+XF group and IL-13+XF+si-PINK1 group. Cell death was evaluated by flow cytometry. Results Compared with the control group, the times of sneezing and the number of nasal scratches in AR group increased significantly. Compared with AR group, the sneezing times and the number of nasal scratches in XF group reduced significantly. In AR group, nasal cilia injury and inflammatory cell infiltration occurred in rats, and XF reduced these pathological changes. Compared with the control group, the expression levels of NLRP3, IL-1β, IL-18, PINK1, Parkin and LC3BII/LC3BI in the nasal mucosa of rats in AR group increased significantly, while the expression of P62 protein decreased significantly. Compared with AR group, the expressions of PINK1, Parkin, LC3BII/LC3BI proteins in the nasal mucosa of XF group were further increased, while the expressions of NLRP3, IL-1β, IL-18 and P62 proteins were significantly decreased. Compared with Con group, the levels of NLRP3, IL-1β, IL-18, PINK1, Parkin and LC3B II/LC3B I in HNEpCs in IL-13 group increased significantly, and the expression of TOM20 protein decreased significantly. Compared with IL-13 group, the expression levels of NLRP3, IL-1β, IL-18, P62 and TOM20 in HNEpCs in IL-13+XF group were significantly decreased, while the expression levels of PINK1, Parkin and LC3B II/LC3B I were further increased. si-PINK1 reversed the protective effect of XF on HNEpCs exposed by IL-13. Conclusion XF may inhibit the activation of NLRP3 inflammatory corpuscles by activating mitochondrial autophagy mediated by PINK1-Parkin, which is helpful to reduce apoptosis and promote the repair of nasal mucosal barrier, thus alleviating AR symptoms.