Mechanism of Modified Shenqi Pill in Treatment of Allergic Rhinitis Comorbid with Asthma Based on Proteomics

To investigate the mechanisms of Modified Shenqi Pill (MSQP) in the treatment of allergic rhinitis comorbid with asthma (ARCA). According to a random number table, 30 BALB/c mice were divided into a control group, an ARCA group, a MSQP low-dose group (MSQP-L, 24.6 g/kg), a MSQP high-dose group (MSQP-H, 49.2 g/kg), and a dexamethasone (DXMS) group (1 mg/kg), with 6 mice in each group. The ARCA mouse model was established using ovalbumin (OVA). MSQP and DXMS were administered by gavage for 10 d. The airway allergic symptom scores, serum OVA-specific immunoglobulin E (OVA-sIgE), histopathological changes in nasal and lung tissues were evaluated. Differential protein expression profiles in lung tissues were detected by proteomics. Functional enrichment analysis of differential proteins was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Activation of the JAK2/STAT1 signaling pathway was assessed by immunohistochemistry (IHC) and Western blot. Activation of B lymphocytes was detected by CD19 and MHC II immunofluorescence (IF) double staining. The proportions of Th1, Th2, and Th17 cells in lung and spleen tissues were analyzed by flow cytometry. Compared with the ARCA group, MSQP significantly decreased airway allergic symptom scores and serum OVA-sIgE levels, and reduced eosinophil infiltration and goblet cell hyperplasia in nasal and lung tissues (P<0.05 or P<0.01). GO and KEGG analyses revealed that differential proteins between MSQP and ARCA groups were primarily associated with immune regulation, involving signaling pathways including JAK/STAT, MHC II-mediated antigen presentation, Th1/Th2 differentiation, and Th17 differentiation. Western blot and IHC results showed that MSQP-H reduced the expressions of JAK2, p-JAK2, STAT1, p-STAT1 in nasal and lung tissues (P<0.01). IF results showed that MSQP-H reduced the numbers of CD19+ and MHC II+ positive cells, and CD19+MHC II+ double-positive cells in nasal and lung tissues (P<0.01). Flow cytometry results showed that MSQP-H changed the proportional relationship among Th1, Th2, and Th17 cells in lung and spleen tissues (P<0.05 or P<0.01). MSQP improved airway allergic symptoms and inflammatory responses in ARCA mice, possibly by inhibiting the activation of JAK2/STAT1 signaling pathway and B lymphocytes, and correcting imbalances in Th1/Th2 and Th17 differentiation.