关键词: 变应性鼻炎, 通窍脱敏方, Th1/Th2, 免疫平衡, Notch信号通路

Abstract: Objective To investigate the mechanism of Tongqiao desensitizing prescription in regulating Th1/Th2 immune imbalance in rats with allergic rhinitis(AR). Method AR rat model was established using ovalbumin(OVA)emulsified with aluminum hydroxide. Following successful model establishment, the rats were allocated into five groups: model group, positive control group(loratadine, 0.9 mg/kg), Tongqiao desensitizing prescription low, medium, and high dose groups(5.54, 11.08, and 22.16 g/kg respectively), and a healthy control group, with 12 rats in each group. Post-modeling, loratadine and the Tongqiao desensitizing prescription were administered via oral gavage once daily for two weeks. Nasal symptoms were recorded and scored. Histopathological changes in the nasal mucosa were examined using hematoxylin and eosin(HE)staining. Serum levels of OVA specific serum immunoglobulin(OVA-sIg)E and IgG1, as well as Th1 cytokines(IL-1, IL-2, TNF-α, TNF-β, IFN-γ)and Th2 cytokines(IL-4, IL-5, IL-6, IL-10, IL-13)in nasal lavage fluid were quantified by ELISA. The ratio of Th1 to Th2 cells in serum was determined by flow cytometry. Expression levels of Notch1, Notch1 intracellular domain(NICD), and Hes1 mRNA and protein in the nasal mucosa were assessed by qRT-PCR and Western bloting analysis. Results Compared with the healthy control group, the nasal mucosal tissue of rats in the model group exhibited pronounced pathological damage, and the nasal symptom scores were significantly elevated(P<0.05). The serum levels of OVA-sIgE and IgG1, as well as the concentrations of IL-4, IL-5, IL-6, IL-10, and IL-13 in nasal lavage fluid, were markedly increased(all P<0.05). Conversely, the ratio of Th1/Th2 cells in the serum and the levels of IL-1, IL-2, TNF-α, TNF-β, and IFN-γ in nasal lavage fluid were significantly reduced(all P<0.05). Additionally, the mRNA and protein expression levels of Notch1, NICD, and Hes1 in the nasal mucosa were notably upregulated(all P<0.05).In comparison to the model group, the histopathological alterations in the nasal mucosa of rats in both the positive control group and the Tongqiao desensitizing prescription dose groups were substantially ameliorated, with a significant decrease in nasal symptom scores(P<0.05). The serum levels of OVA-sIgE and IgG1, along with the concentrations of IL-4, IL-5, IL-6, IL-10, and IL-13 in nasal lavage fluid, were markedly decreased(all P<0.05). Moreover, the ratio of Th1/Th2 cells in the serum and the levels of IL-1, IL-2, TNF-α, TNF-β, and IFN-γ in nasal lavage fluid were significantly elevated(all P<0.05). The mRNA and protein expression levels of Notch1, NICD, and Hes1 in the nasal mucosa were also notably downregulated(all P<0.05). Conclusion Both Tongqiao desensitizing prescription and loratadine are capable of modulating Th1/Th2 immune imbalance and ameliorating nasal mucosal injury and inflammation in AR rats. The underlying mechanism may involve the inhibition of Notch signaling pathway activation.

Key words: Allergic rhinitis, Tongqiao desensitizing prescription, Th1/Th2, Immune balance, Notch signaling pathway