孟鲁司特对过敏性鼻炎大鼠的鼻黏膜重塑作用

Effect of montelukast on nasal mucosa remodeling and Th1/Th2 imbalance in rats with rhinallergosis

目的研究孟鲁司特对过敏性鼻炎大鼠鼻黏膜重塑及辅助T淋巴细胞1(Th1)/辅助T淋巴细胞2(Th2)失衡的作用。方法采用卵清蛋白致敏法建立过敏性鼻炎大鼠模型,将建模成功的大鼠随机分为模型组、实验组及对照组,各10只。另选取10只大鼠为空白组,在上述建模的各时间点均用等量生理盐水干预。实验组大鼠灌胃孟鲁司特15 mg·kg-1,对照组大鼠灌胃地塞米松1 mg·kg-1,对照组与模型组灌胃等量生理盐水,每天1次,连续干预14 d。用酶联免疫吸附(ELISA)法检测大鼠血清及鼻腔灌洗液中白细胞介素-4(IL-4)及干扰素-γ(INF-γ)水平;用苏木精-伊红(HE)染色观察大鼠鼻黏膜组织病理变化;用蛋白质印迹法检测磷酸化氨基末端蛋白激酶(p-JNK)及转化生长因子-β1(TGF-β1)蛋白表达。结果空白组、模型组、实验组和对照组大鼠血清中IL-4分别为(9.85±0.68),(64.67±3.85),(28.53±2.48),(18.96±2.32)pg·mL-1,INF-γ分别为(69.25±4.35),(22.68±3.71),(55.77±4.66),(59.15±2.54)pg·mL-1;鼻黏膜组织HE染色切片中每个视野中嗜酸性粒细胞(EOS)个数分别为(5.36±2.12),(15.63±4.25),(6.58±1.42),(6.21±1.33)个,腺体上皮细胞直径分别为(9.63±0.42),(20.12±2.53),(12.36±2.54),(9.85±0.45)μm;鼻黏膜组织p-JNK相对表达量分别为0.62±0.10,1.02±0.15,0.85±0.11,0.68±0.08,TGF-β1相对表达量分别为0.12±0.03,0.98±0.14,0.82±0.11,0.66±0.10,差异均有统计学意义(均P<0.05)。结论孟鲁司特可降低过敏性鼻炎大鼠血清及鼻腔灌洗液中IL-4及INF-γ水平,调节Th1/Th2细胞因子平衡,同时降低鼻黏膜组织中p-JNK与TGF-β1蛋白表达,延缓鼻黏膜重塑及疾病进展。

Objective To investigate the effects of montelukast on nasal mucosal remodeling and helper T lymphocyte 1(Th1)/helper T lymphocyte 2(Th2)imbalance in rats with rhinallergosis.Methods Rat model of allergic rhinitis was established by ovalbumin sensitization,and the successfully modeled rats were randomly divided into model group,test group and control group,each with 10 rats.Another 10 rats were selected as blank group,treated with the same amount of normal saline while modeling.Rats in test group were administrated with montelukast 15 mg·kg-1,and rats in control group were administrated with dexamethasone 1 mg·kg-1.Blank group and model group were administrated with the same amount of normal saline,once a day for 14 d.Interleukin-4(IL-4)and interferon-γ(INF-γ)in serum and nasal lavage fluid were detected by enzyme-linked immunosorbent assay(ELISA)method;the pathological changes of nasal mucosa in rats were observed by hematoxylin-eosin(HE)staining.The expression of phosphorylated amino-terminal protein kinase(p-JNK)and transforming growth factor-β1(TGF-β1)protein were detected by Western blotting.Results Serum IL-4 in blank group,model group,test group and control group were(9.85±0.68),(64.67±3.85),(28.53±2.48),(18.96±2.32)pg·mL-1,INF-γwere(69.25±4.35),(22.68±3.71),(55.77±4.66),(59.15±2.54)pg·mL-1,the number of EOS in each field of vision in HE stained sections of nasal mucosa were(5.36±2.12),(15.63±4.25),(6.58±1.42),(6.21±1.33),the diameter of glandular epithelial cells were(9.63±0.42),(20.12±2.53),(12.36±2.54)and(9.85±0.45)μm;the relative expression of p-JNK in rat nasal mucosa were 0.62±0.10,1.02±0.15,0.85±0.11 and 0.68±0.08,TGF-β1 were 0.12±0.03,0.98±0.14,0.82±0.11 and 0.66±0.10,all with significant difference(all P<0.05).Conclusion Montelukast can reduce the levels of IL-4 and INF-γin the serum and nasal lavage fluid of rats rhinallergosis,regulate the balance of Th1/Th2 cytokines,and reduce the expression of p-JNK and TGF-β1 in nasal mucosa,delay nasal mucosal remodeling and disease progression.