PPARγ激动剂对变应性鼻炎治疗机制研究

STUDY ON THE MECHANISM OF PPARΓAGONIST FOR ALLERGIC RHINITIS

目的分析过氧化物酶体增殖物激活受体(PPAR)γ激动剂对变应性鼻炎(AR)治疗机制影响。方法BALB/c小鼠60只,随机数字表法将小鼠分为实验组、模型组、正常组与阳性组,除正常组外其他三组小鼠制备AR模型,第14 d起采用10%卵清蛋白(OVA)滴鼻以强化致敏,10μl/鼻,阳性组小鼠每次滴鼻前30 min地塞米松腹腔注射,实验组小鼠PPARγ激动剂吡格列酮(PIO)腹腔注射,持续激发20 d。观察小鼠行为学评分、鼻黏膜通透性与病理形态,血清炎性因子含量、鼻黏膜组织Th1、Th2调控蛋白表达情况。结果模型组小鼠搔鼻与喷嚏次数较正常组升高,阳性组、实验组小鼠搔鼻与喷嚏次数较模型组降低,差异均有统计学意义(均P<0.05);模型组小鼠伊文思蓝含量较正常组升高,阳性组、实验组小鼠伊文思蓝含量较模型组降低,差异均有统计学意义(均P<0.05);模型组小鼠SOCS1、p-STAT6、GATA3蛋白表达较正常组升高,T-bet蛋白表达较正常组降低;阳性组、实验组小鼠SOCS1、p-STAT6、GATA3蛋白表达模型组降低,Tbet蛋白表达较模型组升高,差异均有统计学意义(均P<0.05)。结论PPARγ激动剂经免疫调节可使AR小鼠Th1/Th2失衡逆转,降低血清炎性因子含量与鼻黏膜通透性。

Objective To analyze the effect of peroxisome proliferator-activated receptor(PPAR)γagonist on the treatment mechanism of allergic rhinitis.Methods Sixty BALB/c mice were randomly divided into experimental group,model group,normal group and positive group.In addition to the normal group,the other three groups were used to prepare AR model.From the 14 th day,10%OVA was applied to strengthen the sensitization,10μl/nose.Dexamethasone was injected intraperitoneally 30 min before each nasal drip in the positive group,and PIO was injected intraperitoneally in the experimental group for 20 d.The behavioral score,nasal mucosal permeability and pathological morphology,the content of serum inflammatory factors and the expression of Th1 and Th2 regulatory proteins in nasal mucosa were observed.Results The number of scratching nose and sneezing in the model group was higher than that in the normal group,while that in the positive group and experimental group was lower than that in the model group(P<0.05).The content of Evans blue in the model group was higher than that in the normal group,while that in the positive group and experimental group was lower than that in the model group(P<0.05).SOCS1 in the model group was significantly lower than that in the model group.The expression of SOCS1,p-STAT6 and GATA3 protein in the positive group and experimental group was lower than that in the normal group,and the expression of T-bet protein in the model group was higher than that in the model group(P<0.05).Conclusion PPARγagonists can reverse the Th1/Th2 imbalance of AR mice,reduce serum inflammatory factor content and nasal mucosal permeability through immunomodulation.