乌梅-防风药调控过敏性鼻炎Treg/Th17免疫平衡的分子机制研究  

Study on molecular mechanism of Wumei-Fangfeng drug in regulating Treg/Th17 immune balance in allergic rhinitis

作　　者：孙昭兰 李霞[2] 黄婷婷 相美玲 张凤英[3] SUN Zhaolan;LI Xia;HUANG Tingting;XIANG Meiling;ZHANG Fengying(The First Clinical Medical College of Shandong University of Traditional Chinese Medicine,Jinan 250000,China;Department of Anesthesiology,Weifang Traditional Chinese Medicine,Weifang 262750,China;Department of Otolaryngology,Weifang Traditional Chinese Medicine,Weifang 262750,China)

机构地区：[1]山东中医药大学第一临床医学院,济南250000 [2]潍坊市中医院麻醉科,潍坊262750 [3]潍坊市中医院耳鼻咽喉科,潍坊262750

出　　处：《中国免疫学杂志》2024年第9期1908-1913,共6页Chinese Journal of Immunology

基　　金：潍坊市科技局项目(2021YX022)。

摘　　要：目的:探讨乌梅-防风药调控肥大细胞外泌体源性MMP9对过敏性鼻炎(AR)小鼠Treg/Th17免疫平衡的影响。方法:筛选乌梅与防风的潜在作用靶点,并与AR的风险基因取交集,GO分析与蛋白互作分析筛选出潜在作用靶点。建立AR小鼠模型,分离小鼠股骨中肥大细胞及外泌体。乌梅-防风药及外泌体治疗小鼠。评估各组小鼠行为学评分,检测小鼠鼻黏膜中Foxp3、RORγt的mRNA表达。敲减外泌体中MMP9表达后,观察AR小鼠的行为学评分和Foxp3、RORγt的mRNA表达。结果:生物信息学结果显示,乌梅-防风药可能通过肥大细胞外泌体源性IL-1β、MMP9作用于AR。相对于正常小鼠,AR小鼠Foxp3 mRNA表达降低,RORγt mRNA表达升高,MMP9表达升高(均P<0.05)。乌梅-防风药处理AR小鼠后,Foxp3 mRNA表达升高,RORγt与MMP9表达降低,但肥大细胞外泌体能进一步抵消乌梅-防风药的作用,敲减MMP9后肥大细胞外泌体作用减弱。结论:乌梅-防风药通过抑制骨髓源性肥大细胞外泌体源性MMP9调控AR小鼠Treg/Th17失衡。Objective:To investigate the effects of Wumei-Fangfeng drug on Treg/Th17 immune balance in allergic rhinitis(AR)mice via regulating MMP9 derived from mast cell exosomes.Methods:Potential targets of Wumei and Fangfeng were screened,and the intersection was taken from the targets and AR risk genes,subsequently GO analysis and protein-protein interaction analysis were performed to screen therapeutic targets.AR mice model were constructed,mast cells and exosomes were separate from femurs of mice.Wumei-Fangfeng drug and exosomes were used to treat mice.The behavioral scores of mice in each group were evaluated,mRNA expressions of Foxp3,RORγt were detected in nasal mucosa of mice.After knocking down of MMP9 in exosomes,the behavioral score,Foxp3 and RORγt mRNA expressions were observed in AR mice.Results:Bioinformatics results showed that Wumei-Fangfeng drug may act on AR by mast cell exosomes derived IL-1βand MMP9.Compared with normal mice,mRNA expression of Foxp3 in AR mice was decreased,while RORγt mRNA expression was increased,and MMP9 expression was increased(all P<0.05).Expression of Foxp3 mRNA was increased,and expressions of RORγt and MMP9 were decreased in AR mice treated with Wumei-Fangfeng drug,however,mast cell exosomes could further counteract the effects of Wumei-Fangfeng drug,and the effects of mast cell exosomes was weakened after MMP9 knockdown.Conclusion:Wumei-Fangfeng drug regulates the imbalance of Treg/Th17 in AR mice by inhibiting the exosomal MMP9 of bone marrow-derived mast cells.

关 键 词：乌梅-防风药 肥大细胞外泌体 过敏性鼻炎 MMP9 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]