2,6-DMBQ通过mTOR通路抑制支气管哮喘小鼠气道炎症反应的作用机制  

Mechanism of 2,6-DMBQ attenuates airway inflammatory responses in asthmatic mice via the mTOR signaling pathway

作　　者：李娟 李舒芳 熊晓曼 杨秋雁 谢雪丽 张艳丽[1] LI Juan;LI Shu-Fang;XIONG Xiao-Man;YANG Qiu-Yan;XIE Xue-Li;ZHANG Yan-Li(Department of Pediatrics,Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第三附属医院儿科,河南郑州450052

出　　处：《中国当代儿科杂志》2025年第4期472-479,共8页Chinese Journal of Contemporary Pediatrics

基　　金：河南省重点研发与推广专项(科技攻关)(232102310323)。

摘　　要：目的探究2,6-二甲氧基-1,4-苯醌(2,6-dimethoxy-1,4-benzoquinone,2,6-DMBQ)在哮喘小鼠中的治疗作用及其机制。方法将SPF级BALB/c小鼠随机分为正常对照组、卵清蛋白(ovalbumin,OVA)组、融媒组、布地奈德(budesonide,BUD)组、2,6-DMBQ低、中、高剂量组,每组8只。采用OVA诱导法建立哮喘小鼠模型并给予相应药物干预。使用无创肺功能仪测定小鼠气道高反应性,ELISA法测定支气管肺泡灌洗液中白细胞介素(interleukin,IL)-17、IL-10和血清免疫球蛋白E水平,细胞计数仪检测支气管肺泡灌洗液中嗜酸性粒细胞数,苏木精-伊红染色和过碘酸-希夫染色评估肺组织病理变化,Western blot检测肺组织哺乳动物雷帕霉素靶蛋白通路相关蛋白(p-AKT/AKT、p-p70S6K/p70S6K)表达情况,全自动生化分析仪测定肝肾功能。结果与正常对照组相比,OVA组增强呼吸间歇值、苏木精-伊红染色炎性评分和过碘酸-希夫染色阳性面积、嗜酸性粒细胞百分比、IL-17/IL-10比值、血清免疫球蛋白E水平、p-AKT/AKT和p-p70S6K/p70S6K蛋白相对表达量升高(P<0.05);与OVA组相比,BUD组和2,6-DMBQ中、高剂量组上述指标降低(P<0.05)。结论2,6-DMBQ可抑制哺乳动物雷帕霉素靶蛋白通路减轻哮喘小鼠气道炎症,可能通过减轻辅助性T细胞17/调节性T细胞失衡发挥作用。Objective To investigate the therapeutic effects and mechanisms of 2,6-dimethoxy-1,4-benzoquinone(2,6-DMBQ)in a mouse model of asthma.Methods SPF-grade BALB/c mice were randomly divided into 7 groups(n=8 each group):normal control group,ovalbumin(OVA)group,dimethyl sulfoxide+corn oil group,budesonide(BUD)group,and low,medium,and high dose 2,6-DMBQ groups.An asthma mouse model was established by OVA induction,followed by corresponding drug interventions.Non-invasive lung function tests were performed to measure airway hyperresponsiveness,and enzyme-linked immunosorbent assay was used to determine levels of interleukin(IL)-17,IL-10,and serum immunoglobulin E in bronchoalveolar lavage fluid.A cell counter was employed to detect eosinophil counts in bronchoalveolar lavage fluid,while hematoxylin-eosin staining and periodic acid-Schiff staining were used to assess lung tissue pathological changes.Western blot was conducted to examine the expression of proteins related to the mammalian target of rapamycin pathway(p-AKT/AKT and p-p70S6K/p70S6K),and a fully automated biochemical analyzer was used to evaluate liver and kidney functions.Results Compared with the normal control group,the OVA group showed increased enhanced pause values,inflammation scores from hematoxylin-eosin staining,positive area from periodic acid-Schiff staining,percentage of eosinophils,IL-17/IL-10 ratio,serum immunoglobulin E levels,and relative expression levels of p-AKT/AKT and p-p70S6K/p70S6K(P<0.05).The BUD group and the medium and high dose 2,6-DMBQ groups exhibited decreased values for these indicators compared to the OVA group(P<0.05).Conclusions 2,6-DMBQ can inhibit the mTOR pathway to alleviate airway inflammation in asthmatic mice,possibly by mitigating the imbalance between Th17 and regulatory T cells.

关 键 词：支气管哮喘 2 6-二甲氧基-1 4-苯醌 哺乳动物雷帕霉素靶蛋白通路 Th17/Treg失衡 小鼠 

分 类 号：R285.5[医药卫生—中药学]