%0 Journal Article
%T 树突状细胞Wnt/β-catenin信号通路对哮喘小鼠气道变态反应性炎症的调控作用<br>Regulation of allergic airway inflammation in asthmatic mice by Wnt/β-catenin pathway of dendritic cells
%A 杨
%A 侠
%A 张进召
%A 张
%A 洁
%A 张秋红
%A 刘艳琴
%A 石
%A 婕
%A 张
%A 明
%A 单
%A 虎
%A 李雅莉
%J 西安交通大学学报(医学版)
%D 2017
%R 10.7652/jdyxb201703018
%X 摘要：目的 探讨Wnt/β-catenin信号通路对哮喘小鼠气道变态反应性炎症的调控作用。方法 通过小鼠骨髓细胞诱导分化建立树突状细胞(DCs)体系，并用氯化锂(LiCl)和PKF118-310干预细胞，光镜下观察细胞形态；同种异体混合淋巴细胞反应检测DCs刺激淋巴细胞的增殖能力；Western blot方法检测DCs中GSK-3β和β-catenin蛋白的表达水平。选用BALB/c雌性小鼠为研究对象，使用OVA联合氢氧化铝构建哮喘模型，并用LiCl和PKF干预小鼠，干预结束后收集标本，观察支气管肺泡灌洗液(BALF)中细胞总数和嗜酸性粒细胞百分比；HE染色观察小鼠肺部变态反应性炎症情况；ELISA检测BALF、脾细胞培养上清液中干扰素-γ(IFN-γ)和白介素-4(IL-4)的含量及血清总IgE抗体水平；Western blot检测肺脏组织中Wnt/β-catenin信号通路的重要组分GSK-3β和β-catenin蛋白的表达变化。结果 ①LiCl组DCs对同种异体T细胞的刺激和促增殖能力明显弱于PKF组DCs(P<0.05)；②LiCl组DCs中GSK-3β的蛋白表达水平明显低于PKF组，而其β-catenin的蛋白表达水平显著高于后者(P<0.05)；③动物实验中，与哮喘组相比，LiCl组BALF中白细胞总数和嗜酸性粒细胞百分比均较低，而PKF组与此相反(P<0.05)；④肺组织病理表明，LiCl组肺部炎症程度最轻，PKF组最重(P<0.05)；⑤LiCl组小鼠BALF及脾脏中IL-4水平最低，IFN-γ水平最高；PKF组与此相反，哮喘组介于两者之间(P<0.05)；⑥各组小鼠血清中总IgE含量，与正常对照组比较，实验组IgE显著升高(P<0.05)；LiCl组总IgE水平明显低于哮喘组和PKF组(P<0.05)；⑦LiCl组肺组织中GSK-3β的蛋白表达水平明显低于各组(P<0.05)，而其β-catenin的蛋白表达水平显著高于各组(P<0.05)，PKF组β-catenin的蛋白表达水平明显低于各组(P<0.05)，哮喘组和PKF组之间GSK-3β的蛋白表达水平未见明显差异(P>0.05)。结论 LiCl和PKF118-310可通过调控哮喘小鼠肺组织中Wnt/β-catenin信号通路重要组分GSK-3β和β-catenin的蛋白表达而改变哮喘严重程度，为哮喘的治疗提供了新方向。<br>ABSTRACT: Objective To investigate the role of Wnt/β-catenin pathway in regulating allergic airway inflammation in asthmatic mice. Methods We induced dendritic cells (DCs) from bone marrow of BALB/c mice, and then treated the cells with LiCl and PKF118-310, separately. We observed the morphological features of DCs under light microscope. Mixed lymphocyte reaction (MLR) was used to observe the functional changes of DCs. Western blot was used to detect the expressions of GSK-3β and β-catenin at the protein level. We established a mouse asthma model by using ovalbumin (OVA), and then treated these mice with LiCl and PKF118-310. The total number of cells and eosinophil percentage in BALF were determined. The lungs of mice were observed by HE staining to evaluate the degree of allergic inflammation. The cytokines in BALF and spleen cells supernatant were assayed by enzyme-linked immunoassay (ELISA), and the total IgE in the serum was also measured by ELISA. The protein expression levels of GSK-3β and β-catenin in lung tissue were assayed by Western blot. Results ① The DCs treated with LiCl promoted the proliferation of allogeneic T lymphocytes in MLR more weakly than those treated with PKF118-310 (P<0.01). ② The GSK-3β protein expression level of DCs treated with LiCl was significantly lower than DCs treated with PKF118-310. In contrast, the β-catenin protein expression of DCs treated with LiCl was higher than that of DCs treated with PKF118-310 (P<0.01). ③ The total number of cells and eosinophil percentage in BALF
%K 树突状细胞
%K Wnt/β-catenin通路
%K 氯化锂
%K PKF118-310
%K 哮喘&lt
%K br&gt
%K dendritic cell
%K Wnt /β-catenin pathway
%K LiCl
%K PKF118-310
%K asthma
%U http://yxxb.xjtu.edu.cn//oa/darticle.aspx?type=view&id=201703018