18β-甘草次酸钠对变应性鼻炎大鼠鼻黏膜TNF-α的干预作用

Effects of 18β-sodium glycyrrhetinic acid on TNF-α expression in rats with allergic rhinitis

目的:观察18β-甘草次酸钠(18β-SGA)对变应性鼻炎(AR)大鼠鼻黏膜肿瘤坏死因子-α(TNF-α)表达的影响,探讨18β-SGA对AR的干预机制。方法:106只SPF级Wistar大鼠随机分为空白对照组、AR组、布地奈德组、18β-SGA低剂量组和18β-SGA高剂量组。经卵清蛋白构建AR大鼠模型后给予药物干预,各组大鼠分别在干预2周和4周后处死,取大鼠鼻黏膜行免疫组织化学染色、RT-PCR和免疫蛋白印迹定位、定量大鼠鼻黏膜中TNF-α表达。结果:经免疫组织化学、免疫印迹及RT-PCR发现,与空白对照组相比,AR组大鼠鼻黏膜中TNF-α高表达于鼻黏膜纤毛柱状上皮、血管内皮、腺体及部分炎症细胞胞质中(P<0.01)。经不同剂量的18β-SGA干预后,TNF-α表达量明显下降(P<0.01),尤以18β-SGA低剂量组干预4周后效果最明显(P<0.01)。结论:不同剂量的18β-SGA对AR有治疗作用,且其发挥作用的机制与抑制TNF-α的高表达有关。

Objective:To observe the effect of 18β-sodium glycyrrhetinic acid(18β-SGA)on the expression of TNF-αin nasal mucosa of rats with allergic rhinitis(AR),and explore the intervention mechanism of 18β-SGA on AR.Method:One hundred and six SPF-level Wistar rats were randomly divided into control group,AR group,budesonide group,18β-SGA low dose group and high dose group.After the AR rat model was constructed by ovalbumin,the rats were given drug intervention and sacrificed after 2 and 4 weeks of intervention.The nasal mucosa of the rats was taken for immunohistochemical staining,RT-qPCR and Western-blotting to localize and quantify the expression of TNF-α.Result:By immunohistochemistry,Western-blotting and RT-PCR,TNF-αwas mainly found in the columnar epithelium,vascular endothelium,glandular and some inflammatory cytoplasm of nasal mucosa.And the expression of TNF-αin the nasal mucosa of AR rats was significantly increased than the normal group at the protein and mRNA levels(P<0.01).After intervention with different doses of 18β-SGA,the expression of TNF-αwas significantly decreased(P<0.01),especially after 4 weeks of 18β-SGA low dose group(P<0.01).Conclusion:Different doses of 18β-SGA have therapeutic effects on AR,and its mechanism of action may be related to the inhibition of TNF-αexpression.