OBJECTIVE To explore the potential mechanism of Yiqi Wenyang Recipe in the intervention of allergic rhinitis (AR) mice.

METHODS C57/BL6 mice were randomly divided into blank, model, Yiqi Wenyang Recipe and Yiqi Wenyang Recipe+EX-527 Sirtuin 1 (SIRT1) inhibitor groups. The AR model of mice was established by ovalbumin based challenge sensitization method, each group received corresponding intervention measures. Assessment of behavioral changes in mice; nasal mucosal lesions were observed by HE and toluidine blue staining; the serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), and immunoglobulin E (IgE) were measured by ELISA; the expression levels of phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 6 (p-STAT6), phospho-dynamin-related protein 1 (p-Drp1), SIRT1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in nasal mucosa were determined by Western blot combined with immunofluorescence; reactive oxygen species (ROS) levels were detected by fluorescent probe method; the morphological changes of mitochondria in the microstructure of nasal mucosa were observed by transmission electron microscopy.

RESULTS Compared with the blank group, the frequency of scratching and sneezing in the model group was significantly increased, and a large number of eosinophils and mast cells were found in the nasal mucosa (P < 0.05); compared with the model group, the nasal allergic symptoms and the level of nasal mucosal inflammatory reaction in the Yiqi Wenyang Recipe group were significantly improved (P < 0.05); compared with the Yiqi Wenyang Recipe group, the scratching and sneezing of mice in the Yiqi Wenyang Recipe+EX-527 group increased again, and the counts of eosinophils and mast cells in nasal mucosa increased significantly (P < 0.05). Compared with the model group, the levels of serum IL-4 and IgE in the Yiqi Wenyang Recipe group decreased, while the level of serum IFN-γ increased (P < 0.05); the serum IL-4 and IgE of mice in the Yiqi Wenyang Recipe+ex-527 group were significantly higher than those in the Yiqi Wenyang Recipe group (P < 0.05). Western blot and immunofluorescence showed that Yiqi Wenyang Recipe could effectively inhibit the increase of p-JAK2, p-STAT6, p-Drp1(ser616) levels induced by ovalbumin sensitization, as well as the decrease of SIRT1 and PGC-1 α expression(P < 0.01); however, the intervention of EX-527 significantly blunted the regulatory effect of Yiqi Wenyang Recipe on the above signaling molecules(P < 0.05, P < 0.01). The results of transmission electron microscopy and fluorescent probe showed that in the model group, a large number of spherical mitochondria were found in the mitochondria of nasal mucosa, and the level of ROS was significantly increased(P < 0.01);; the intervention of Yiqi Wenyang recipe effectively restored the long tubular morphology of mitochondria and reduced ROS level(P < 0.01);, while the intervention of EX-527 weakened the above improvement effect(P < 0.01).

CONCLUSION Yiqi Wenyang Recipe can regulate SIRT1 to activate PGC-1α, and then inhibit Drp1 mediated excessive mitochondrial fission to intervene AR; SIRT1 may be one of the important targets of Yiqi Wenyang Recipe in the intervention of AR.