胰高血糖素样肽-1调节Th细胞分化对屋尘螨诱导小鼠过敏性气道炎症的影响

Effect of glucation-like pepside-1 on house dust mite-induced allergic airway inflammation in mice by regulating Th polarization

目的探讨胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)对屋尘螨(house dust mite,HDM)诱导小鼠过敏性气道炎症的作用,并探讨其作用机制。方法将24只SPF级C57 BL6小鼠随机分为对照(Con)组、GLP-1组、屋尘螨(HDM)组、屋尘螨+GLP-1(HDM+GLP-1)组。用HDM建立小鼠过敏性哮喘模型,选用临床常用的GLP-1类似物利拉鲁肽干预小鼠。HDM组,给予鼻腔滴注HDM诱导小鼠气道过敏性炎症,并给予等体积生理盐水皮下注射;HDM+GLP-1组,给予HDM鼻腔滴注,同时给予利拉鲁肽皮下注射;GLP-1组,给予利拉鲁肽皮下注射,并给予等体积生理盐水鼻腔滴注;Con组给予等体积生理盐水鼻腔滴注及皮下注射。通过HE染色观察肺组织病理学变化,流式细胞仪检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中不同Th细胞的比例,ELISA检测IL-4、IL-5、IL-13炎性因子的浓度。结果HDM组小鼠肺组织病理损伤明显,GLP-1抑制屋尘螨诱导的小鼠气道过敏性炎症,降低Th2细胞比例(Th2,CD4+IL-4+:HDM 20.2±2.06%vs.HDM+GLP-19.57±3.66%,P<0.05),促进Th1 Th2细胞平衡。结论GLP-1负向调节Th2细胞形成,促进T细胞向Th1细胞方向分化,从而抑制屋尘螨诱导的小鼠气道过敏性炎症。

Objective To explore the effect of Glucagon-like peptide-1(GLP-1)on airway allergic inflammation induced by house dust mite(HDM)in mice and to investigate its mechanism.Methods C57 BL6 SPF mice(n=24)were randomly divided into four groups,including control(Con),GLP-1,HDM,and HDM+GLP-1 group.Allergic asthma model was established using HDM in mice.Mice were intervened by liraglutide,a commonly used GLP-1 analogue.HDM was given intranasally to induce allergic airway inflammation and subcutaneous injection with same volume of saline were performed in HDM group.HDM was given intranasally and liraglutide was given subcutaneously in HDM+GLP-1 group.Liraglutide was injected subcutaneously and equal volume of saline was given intranasally in GLP-1 group.Equal volume of saline were given intranasally and subcutaneously respectively in control group.Pathological changes of lung tissue were observed under hematoxylin-eosin staining,proportions of different Th cells in bronchoalveolar lavage fluid(BALF)were detected by flow cytometry,and concentrations of inflammatory factors including IL-4,IL-5,and IL-13 were measured using ELISA methods.Results Compared with the other three groups,most severe pathological damage of lung tissue was shown in HDM group.Airway allergic inflammation induced by HDM was suppressed by GLP-1,while proportion of Th2 cells decreased(Th2,CD4+IL-4+:HDM 20.2±2.06%vs.HDM+GLP-19.57±3.66%,P<0.05)and balance of Th1 Th2 cells was promoted as the effect of GLP-1.Conclusions The formation of Th2 cells was regulated negatively and the differentiation of T cells was promoted towards Th1 cells by GLP-1.Thereby,allergic airway inflammation induced by HDM in mice was inhibited by GLP-1.