浙江医学2017，Vol.39Issue(11)：860-864,870,6.DOI:10.12056/j.issn.1006-2785.2017.39.11.2017-19
雷帕霉素对哮喘缓解期小鼠模型气道炎症的作用
Effects of rapamycin on airway inflammation in mice with asthma during remission
摘要
Abstract
Objective To investigate the effects of rapamycin on airway inflammation in mice with asthma during remission.Methods Fifty Balb/c mice were randomly divided into 5 groups:normal control,asthma,asthma in remission,dexamethasone and rapamycin groups with 10 mice in each group.The asthma model was induced by ovalbumin (OVA) sensitization and challenge;after 3-week interval the mice were challenged by OVA again.Dexamethasone,rapamycin or saline was given to 3 groups,respectively during 3-week interval.Airway reactivity was measured by Buxco's non-invasive system.Cytokines IL-4,IL-5,IL-13,IL-17 and INF-γ in bronchoalveolar lavage fluid (BALF) were assessed by Luminex method.Lung tissues were examined for inflammatory cell infiltration.The expression of p-S6,S6,AKT and p-AKT (S473) in lung tissue was examined by Western blot.CD4+CD25+Foxp3+ Treg cells in BALF was assessed by flow cytometry.Results Compared with the normal and remission groups,OVA re-expose significantly increased airway hyperresponsiveness(P＜0.01),elevated IL-4,IL-5,IL-13,IL-17 levels (P＜0.01),and reduced INF-γ in the BALF (P＜0.01);it also markedly increased inflammatory cells in lung tissue,increased Ttreg cells in BALF and decreased expression of p-S6(P＜0.01).Rapamycin significantly reduced airway hyperresponsiveness to aerosolized methacholine at 6.25mg/ml(P＜0.01),inhibited IL-4 level in BALF,and markedly decreased inflammatory infiltration in lung tissues(P＜0.01).Notably,rapamycin significantly inhibited the expression of p-S6;and also Treg cells in BALF were significantly reduced after rapamycin treatment.Conclusion Antiasthmatic effects of rapamycin during remission time are at least partially through mTORC1 signaling pathway,and rapamycin may be used for asthma patients in remission to control asthma attack.关键词
雷帕霉素/哮喘/mTOR信号通路Key words
Rapamycin/Asthma/mTOR signaling pathway引用本文复制引用
金华良,王利民,王娇莉,夏俊波,马胜林..雷帕霉素对哮喘缓解期小鼠模型气道炎症的作用[J].浙江医学,2017,39(11):860-864,870,6.基金项目
国家自然科学基金(81403247/H2902) （81403247/H2902）
浙江省医药卫生科技项目(2014KYA170) （2014KYA170）
