【摘要】 目的:探讨支气管哮喘中的分泌型磷脂酶A2-X(sPLA2-X)与嗜酸性粒细胞的关联,为支气管哮喘的治疗提供新的思路与策略。方法:SPF级6～8周雌性BABL/c小鼠48只,分为4组,每组12只,分为健康对照组、哮喘对照组、哮喘/嗜酸性粒细胞删除组及哮喘/嗜酸性粒细胞删除同型对照组。构建小鼠支气管哮喘模型,除健康对照组小鼠于0、7、14 d腹腔注射生理盐水外,其余组小鼠每只分别于0、7、14 d腹腔注射50μg OVA与2 mg氢氧化铝凝胶(溶于200μL生理盐水)。随后根据分组于第21和26天分别进行嗜酸性粒细胞删除抗体(anti-CCR3)及同型对照的腹腔注射及吸入麻醉后的删除抗体滴鼻。于雾化结束后48 h内完成小鼠肺功能检测,每组小鼠一半行全肺灌洗、一半用于肺组织切片HE染色,全血用于检测血清IgE,肺泡灌洗液(BALF)上清液应用于检测细胞因子,肺泡灌洗液细胞用于细胞总数、细胞分类及流式分析。结果:(1)与哮喘对照组相比,哮喘/嗜酸性粒细胞删除组小鼠的气道、肺泡炎症反应显著减轻。(2)哮喘/嗜酸性粒细胞删除组(OVA/anti-CCR3)支气管肺泡灌洗液中嗜酸性粒细胞的百分比显著降低(P<0.05)。(3)与哮喘对照组比较,哮喘/嗜酸性粒细胞删除组小鼠气道高反应显著降低(P<0.05)。(4)与哮喘对照组相比,哮喘/嗜酸性粒细胞删除组小鼠BALF上清与血清中的sPLA2-X水平均显著降低(P<0.05)。(5)与哮喘对照组对比,哮喘/嗜酸性粒细胞删除组小鼠BALF上清中的IL-4、IL-5和IL-13水平显著降低,血清中IgE的水平也显著降低(P<0.05)。结论:支气管哮喘中嗜酸性粒细胞与sPLA2-X有重要的关联。更多还原

【Abstract】 AIM:To investigate the association between soluble phospholipase A2-X(sPLA2-X)and eosinophils in bronchial asthma,and to provide new insight and strategies for the treatment of bronchial asthma.METHODS:Female Babl/c mice(n=48)of SPF grade and 6～8 weeks old were divided into 4 groups(with 12 in each group:healthy control group,asthma control group,eosinophil deletion group,and asthma/eosinophil deletion isotype control group).The mouse model of bronchial asthma was constructed.The mice in healthy control group were intraperitoneally injected with saline on days 0,7,and 14.The mice in other groups were intraperitoneally injected with 50 μg OVA and 2 mg aluminum hydroxide gel(soluble in 200 μL saline.On the 21 st d and 26 th d,eosinophil deletion antibody(anti-CCR3)and isotype control were intraperitoneally injected and intranasally respectively,and then the lungs function test was conducted within 48 h after the end of nebulization.Half of the mice in each group were subjected to whole lung lavage,the remaining half were used for lung tissue section with HE staining,the whole blood was used to measure serum IgE,the supernatant of broncho alveolar lavage fluid(BALF)was used to measure cytokines,and total number of cells in the bronchoalveolar lavage fluid was analyzed for cell classification and flow cytometry.RESULTS:(1)Compared with asthma control group,the airway and alveolar inflammatory responses in asthma/eosinophil deletion group was significantly alleviated.(2)Compared with asthma control group,anti-CCR3 successfully deleted eosinophils,and the percentage of eosinophils in bronchoalveolar lavage fluid in asthma/eosinophil deletion group was significantly reduced(P<0.05).(3)The airway hyperresponsiveness in asthma/eosinophil deletion group was significantly decreased as compared with asthma control group(P<0.05).(4)The levels of sPLA2-X in the serum and BALF was significantly reduced in asthma/eosinophil deletion group as compared with asthma control group(P<0.05).(5)Compared with asthma control group,the levels of IL-4,IL-5,and IL-13 in the BALF of the mice in asthma/eosinophil deletion group were significantly reduced,and the serum level of IgE was also decreased(P<0.05).CONCLUSION:Eosinophils in bronchial asthma are importantly associated with sPLA2-X.更多还原