摘要
目的探讨粉尘螨抗原纳米疫苗PLGA-Der f2免疫治疗小鼠过敏性哮喘的疗效及机制。方法使用PLGA包裹重组粉尘螨抗原Der f2构建纳米疫苗PLGA-Der f2。将雌性BALB/c小鼠随机分为空白对照组(PBS组,n=32)和致敏组(n=32),致敏组再分为哮喘模型组(Asthma组,n=8)、空纳米对照组(PLGA组,n=8)、重组粉尘螨抗原Der f2免疫治疗组(Der f2组,n=8)、PLGA-Der f2纳米疫苗免疫治疗组(PLGA-Der f2组,n=8)。使用粉尘螨粗提液分别对致敏组各组BALB/c小鼠进行致敏、激发,检测各组小鼠气道高反应性;通过HE染色观察小鼠肺部炎症浸润情况;比较小鼠支气管肺泡灌洗液(BAL F)中细胞总数和嗜酸性粒细胞数量;使用酶联免疫吸附测定法测定小鼠肺组织研磨上清及脾细胞培养上清中的细胞因子IL-4、IL-13以及血清中的尘螨抗原特异性IgE抗体(sIgE)。结果与Asthma组和PLGA组相比:Der f2组和PLGA-Der f2组小鼠气道高反应性Penh值明显降低(均P<0.05),肺部炎症浸润显著减轻;BAL F中细胞总数(P<0.05)、嗜酸性粒细胞数量减少(P<0.05),血清中抗sIgE显著降低(P<0.05);肺组织研磨上清和脾细胞培养上清中IL-4、IL-13均明显降低(均P<0.05)。与粉尘螨抗原Der f2相比,PLGA-Der f2纳米疫苗治疗作用更强(均P<0.05)。结论粉尘螨抗原PLGA-Der f2纳米疫苗免疫治疗作用强于单独使用粉尘螨抗原Der f2。
Objective To investigate the efficacy and mechanism of dust mite antigen nano vaccine PLGA-Der f2 in the treatment of allergic asthma in mice.Methods The nano vaccine PLGA-Der f2 was constructed by using PLGA to encapsulate the recombinant dust mite antigen Der f2.Female BALB/c mice were randomly divided into PBS group(n=32),asthma model group(asthma group,n=8),vaccine control group(PLGA group,n=8),Der f2 immunotherapy group(Der f2 group,n=8),and PLGA-Der f2 nano vaccine immunotherapy group(PLGA-Der f2 group,n=8).The BALB/c mice were sensitized and challenged with the crude extract of dust mites.The airway hyperresponsiveness and numbers of total cells and eosinophils in bronchoalveolar lavage fluid(BAL F)were measured.In addition,pulmonary inflammatory infiltration was evaluated by H&E staining,and concentrations of IL-4 and IL-13 in lung homogenate and spleen cell culture supernatant and levels of dust mite-specific IgE antibody(sIgE)in serum were determined by enzyme-linked immunosorbent assay.Results Compared with asthma and PLGA groups,Penh values,pulmonary inflammatory infiltration,numbers of total cells and eosinophils in BAL F,serum levels of sIgE and concentrations of IL-4 and IL-13 in lung homogenate and spleen cell culture supernatant significantly decreased in both Der f2 and PLGA-Der f2 groups(P<0.05).Moreover,PLGA-Der f2 nano vaccine had a stronger therapeutic effect than dust mite antigen Der f2(P<0.05).Conclusion Dust mite antigen PLGA-Der f2 nano vaccine is superior to dust mite antigen Der f2 for treating allergic asthma.
作者
王俊轶
肖小军深圳大学医学部过敏反应与免疫学研究所
何翔
张雷
冉琴
胡玲娟
刘志刚
李国平
WANG Jun-yi;XIAO Xiao-jun;HE Xiang;ZHANG Lei;RAN Qin;HU Ling-juan;LIU Zhi-gang;LI Guo-ping(Department of Respiratory and Critical Care Medicine,Chengdu Institute of Respiratory Health,the Third People’s Hospital of Chengdu,Chengdu 610000,China;Allergy&Inflammation Research Unit,Chengdu Institute of Respiratory Health,the Third People’s Hospital of Chengdu,Chengdu 610000,China;Research Center of Allergy&Immunology,Shenzhen University School of Medicine,Shenzhen 510182,China;st Department of Respiratory Medicine,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)
出处
《南昌大学学报（医学版）》
CAS
2019年第5期1-5,11,共6页
Journal of Nanchang University：Medical Sciences
基金
国家重点研发计划“精准医学研究”项目(2016YFC0905802)
国家自然科学青年基金(31700805)
四川省卫生和计划生育委员会科研课题(18PJ403)
