细粒棘球绦虫分泌抗原B调控Th17/Treg抑制过敏性哮喘的研究  

Antigen B secreted by Echinococcus granulosus reduces asthma by rebalancing Th17/Treg

作　　者：张耀 齐文静 焦红杰 吴川川 郭刚 任远 李军 况玲[1] 张文宝 ZHANG Yao;QI Wen-jing;JIAO Hong-jie;WU Chuan-chuan;GUO Gang;REN Yuan;LI Jun;KUANG Ling;ZHANG Wen-bao(College of Veterinary Medicine,Xinjiang Agricultural University,Urumqi 830052,China;State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medicine Institute,the First Affiliated Hospital of Xinjiang Medical University)

机构地区：[1]新疆农业大学动物医学学院,新疆乌鲁木齐830052 [2]中亚高发病成因与防治国家重点实验室,临床医学研究院,新疆医科大学第一附属医院

出　　处：《中国病原生物学杂志》2021年第8期927-930,933,共5页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.81830066)。

摘　　要：目的探讨细粒棘球蚴分泌抗原B(EgAgB)对过敏性哮喘的抑制作用及其机制。方法将32只小鼠随机分为4组(每组8只),其中A组为高剂量干预组(HAgB:20μg EgAgB+OVA),B组为低剂量干预组(LAgB:2μg EgAgB+OVA),C组为过敏性哮喘组(OVA),D组为PBS对照组。采用ELISA法检测小鼠抗体水平;HE、PAS组织染色检测小鼠肺组织病理变化及黏蛋白分泌水平;利用流式细胞术分析肺脏和脾脏组织中淋巴细胞的分群及活化比例。结果 EgAgB免疫小鼠血IgG、IgM和IgG2b抗体水平显著高于PBS对照组(D组)(P<0.01),IgG1、IgG2a和IgE水平与PBS对照组(D组)相比差异无统计学意义(均P>0.05);HE、PAS染色显示,EgAgB接种组与C组相比能够显著抑制小鼠气道炎症及气道粘液的分泌(均P<0.01);流式细胞术检测显示,免疫高剂量EgAgB组小鼠肺组织及脾脏组织嗜酸性粒细胞和Th17的数量显著减少(均P<0.01),Treg数量显著增多(P<0.01)。结论 EgAgB能够通过调节宿主免疫平衡抑制过敏性哮喘,可作为防治自身免疫性疾病和过敏性疾病的候选小分子蛋白。Objective The current authors previously found that an infection with Echinococcus granulosus larvae reduced ovalbumin-induced asthma. The current study will further determine whether the E. granulosus antigen B(EgAgB) has a similar effect on airway inflammation. Methods BALB/c mice(n=32) were randomly divided into 4 groups with 8 mice in each group including a PBS control group, an ovalbumin(OVA) group, a high-dose EgAgB group(HAgB:20μg EgAgB+OVA), and a low-dose EgAgB group(LAgB:2μg EgAgB+OVA). Each of the mice in the two EgAgB groups was intraperitoneally vaccinated for 5 days. The mice were sensitized and challenged with OVA one day after the last vaccination. ELISA was used to detect the levels of anti-EgAgB antibodies in the sera of the mice. Hematoxylin & eosin(HE) staining and periodic acid-Schiff(PAS) staining were used to identify pathological changes and determine levels of mucin secretion. Flow cytometry was used to analyze changes in lymphocyte populations in lung and spleen tissues. Results The levels of IgG, IgM, and IgG2 b antibodies in mice immunized with EgAgB were markedly higher than those in the OVA group(P<0.001), whereas there was no difference in levels of IgG1, IgG2 a, and IgE antibodies between vaccinated mice and the OVA group. HE and PAS staining indicated that EgAgB markedly inhibited airway inflammation and mucus secretion in the lungs of the mice(P<0.001). Flow cytometry indicated that eosinophils markedly decreased in the lung and spleen of mice in the EgAgB group compared to those in the OVA group. The number of Th17 cells decreased and the number of Treg cells increased(P<0.001). Conclusion EgAgB suppresses airway inflammation in the lungs by regulating the host immune responses. A small molecule protein, EgAgB may be used for the prevention and treatment of airway inflammation.

关 键 词：细粒棘球绦虫 棘球蚴(包虫) EgAgB 哮喘 TH17/TREG 

分 类 号：R383.33[医药卫生—医学寄生虫学]