Effect of RORC inhibitor on HIF-1α and VEGF in nasal mucosa of allergic rhinitis of mice / 中华耳鼻咽喉头颈外科杂志

ABSTRACT

Objective@#To investigate the effects of the retinoic acid receptor related orphan C (RORC) inhibitor (SR1001) on the expression changes of proteins of hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF) in the nasal mucosa of mice with allergic rhinitis (AR) model.@*Methods@#Thirty BALB/c were randomly divided into normal group, AR model group and RORC inhibitor group, 10 mice each group. AR model of mice was established by ovalbumin (OVA) sensitization method. RORC inhibitor group was given intraperitoneal injection of SR1001 (25 mg/kg), while AR model group intraperitoneal injection of the same volume of 0.9% normal saline. The symptom score of the mice was determined every weekend after administration. The pathological morphological changes in the nasal mucosa tissue obtained from anesthetized mice were observed by light microscope. The expression of HIF-1α and VEGF protein were detected by immunohistochemistry. IFN-γ, IL-17, and sIgE in the serum were detected by ELISA and the expression of HIF-1α and VEGF in the nasal mucosal tissue of the mice were measured by Western blot. One-way ANOVA was used for inter-group comparison. LSD method was used for inter-group comparison with equal variance, and Dunnett T3 method for inter-group comparison with unequal variance. P<0.05 was considered statistically significant.@*Results@#The AR model was successfully established. Compared with the model group, the RORC inhibitor group significantly reduced the symptom score of AR mice (4.02±0.97 vs 8.50±1.76, t=7.050, P<0.01). The damaged mucosal epithelium appeared to be improved, the glands and dilated ducts tended to be normal, the mast goblet cells significantly reduced, and the infiltration of inflammatory cells in the inherent mucosa reduced. Meanwhile, the content of IL-17 and sIgE in serum decreased [(25.10±4.11) ng/ml vs (42.56±5.98) ng/ml, (0.875±0.244) ng/ml vs (1.982±0.365) ng/ml, t value was 14.141, 10.275, respectively, all P<0.01] and the content of IFN-γ increased [(61.32±8.83) pg/ml vs (38.94±5.97) pg/ml, t=8.133, P<0.01]. The expression of HIF-1α and VEGF protein in the nasal mucosal tissues of AR mice significantly reduced (0.92±0.08 vs 1.67±0.31, 1.12±0.21 vs 2.54±0.46, t value was 7.408, 8.880, respectively, all P<0.01).@*Conclusion@#The RORC inhibitor has the therapeutic effect on AR by changing the content of inflammatory factors in AR mice and reducing the expression level of HIF-1α and VEGF in the nasal mucosa.