通窍脱敏方介导Notch信号通路调控变应性鼻炎大鼠Th1/Th2免疫失衡的作用机制  

Mechanism of Tongqiao desensitization prescription mediated Notch signaling pathway on regulating Th1/Th2 immune imbalance in allergic rhinitis rats

作　　者：马凤梅[1] 荣婷 马蕴蕾[2] MA Fengmei;RONG Ting;MA Yunlei(Otolaryngology Department,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050017,Hebei,China;Respiratory Intensive Care Department,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050017,Hebei,China)

机构地区：[1]河北省中医院耳鼻喉科,河北石家庄050017 [2]河北省中医院呼吸重症科,河北石家庄050017

出　　处：《山东大学学报(医学版)》2025年第3期55-62,70,共9页Journal of Shandong University:Health Sciences

基　　金：河北省中医药管理局2023年度中医药类科学研究课题(2023028)。

摘　　要：目的探讨通窍脱敏方调控变应性鼻炎(allergic rhinitis,AR)大鼠Th1/Th2免疫失衡的作用机制。方法采用鸡卵白蛋白(ovalbumin,OVA)混合氢氧化铝制备AR大鼠模型,造模成功后将大鼠分为AR模型组、阳性对照组(氯雷他定,0.9 mg/kg)、通窍脱敏方低、中、高剂量组(5.54、11.08、22.16 g/kg),另设健康对照组,每组12只。造模后,给予相应剂量的氯雷他定和通窍脱敏方灌胃干预,1次/d,连续2周。记录大鼠鼻部症状并评分;采用苏木精-伊红染色观察鼻黏膜组织病理学变化;ELISA检测血清中OVA特异性血清免疫球蛋白(OVA-specific serum immunoglobulin,OVA-sIg)E、IgG1水平以及鼻灌洗液中Th1细胞因子白细胞介素(interleukin,IL)-1、IL-2、肿瘤坏死因子(tumor necrosis factor,TNF)-α、TNF-β、干扰素(interferon,IFN)-γ和Th2细胞因子IL-4、IL-5、IL-6、IL-10、IL-13水平;流式细胞术检测血清中Th1/Th2细胞比率;采用qRT-PCR法和Western blotting法检测鼻黏膜组织中Notch1、Notch1胞内域(Notch1 intracellular domain,NICD)、Hes1 mRNA和蛋白表达水平。结果与健康对照组相比,AR模型组大鼠鼻黏膜组织损伤严重,鼻部症状评分明显升高(P<0.05);血清中OVA-sIgE、IgG1水平以及鼻灌洗液中IL-4、IL-5、IL-6、IL-10、IL-13水平显著升高(P均<0.05),血清中Th1/Th2细胞比率以及鼻灌洗液中IL-1、IL-2、TNF-α、TNF-β、IFN-γ水平显著降低(P均<0.05);鼻黏膜组织中Notch1、NICD、Hes1 mRNA和蛋白表达水平显著升高(P均<0.05)。与AR模型组相比,阳性对照组和通窍脱敏方各剂量组大鼠鼻黏膜组织病理学改变明显改善,鼻部症状评分明显降低(P<0.05);血清中OVA-sIgE、IgG1水平以及鼻灌洗液中IL-4、IL-5、IL-6、IL-10、IL-13水平显著降低(P均<0.05),血清中Th1/Th2细胞比率以及鼻灌洗液中IL-1、IL-2、TNF-α、TNF-β、IFN-γ水平显著升高(P均<0.05);鼻黏膜组织中Notch1、NICD、Hes1 mRNA和蛋白表达水平显著降低(P均<0.05)。结论通窍脱�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-γin 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 contr

关 键 词：变应性鼻炎 通窍脱敏方 Th1/Th2 免疫平衡 NOTCH信号通路 

分 类 号：R765[医药卫生—耳鼻咽喉科]