摘要
目的探讨穗花杉双黄酮(AF)对哮喘幼年大鼠气道炎症的影响并初步探讨其机制。方法采用腹腔注射联合雾化吸入卵白蛋白(OVA)法诱导幼年SD大鼠建立哮喘模型,将大鼠随机分为哮喘模型(M)组、地塞米松(DXMS)组、AF低(AF L)、中(AF M)、高(AF H)剂量组和正常对照(CT)组。给药结束后,无创肺功能仪检测气道反应性,通过吉姆萨(Giemsa)染色分析支气管肺泡灌洗液(BALF)中炎性细胞类型并计数,使用苏木素-伊红(HE)染色评价肺组织和支气管组织病理特征,酶联免疫吸附剂实验(ELISA)检测血清炎症因子的含量,Western blot检测肺组织GMP-AMP合酶(cGAS)、干扰素基因刺激物(STING)、磷酸化-干扰素调节因子3(p-IRF3)和干扰素调节因子3(IRF3)蛋白表达。结果与CT组相比,M组幼年大鼠肺组织和支气管组织可见明显病理损伤,气道反应性、肺组织、支气管组织病理评分、BALF中炎性细胞总数及单核细胞、嗜酸性粒细胞、中性粒细胞和淋巴细胞的数量显著增加、血清炎症因子以及肺组织c GAS、STING、p-IRF3/IRF3蛋白表达显著增加(P<0.05);与M组相比,DXMS和高剂量AF治疗哮喘大鼠后肺、支气管组织病理损伤缓解,气道反应性、肺组织、支气管组织病理评分、BALF中炎性细胞总数显著降低、血清炎症因子以及肺组织c GAS、STING、p-IRF3/IRF3蛋白表达明显降低(P<0.05)。结论AF可缓解哮喘幼年大鼠的气道炎症,其可能是通过抑制cGAS-STING信号通路实现的。
The aim of this study was to investigate the effect of amentoflavone(AF)on airway inflammation in asthmatic young rats and its mechanism.The asthmatic model of young SD rats was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).The rats were randomly grouped into asthma model(M)group,dexamethasone(DXMS)group,AF low(AF L),AF medium(AF M),AF high(AF H)dose group and normal control group(CT)group.After administration,the airway reactivity was detected with non-invasive lung function instrument and the inflammatory cell types in bronchoalveolar lavage fluid(BALF)were analyzed and counted by Giemsa staining.Furthermore,hematoxylin-eosin(HE)staining was applied to evaluate the pathological morphology of lung and bronchial tissues,enzyme-linked immunosorbent assay(ELISA)kits were used to detect the content of inflammatory factors in serum,Western blot was applied to detect the protein expression of GMP-AMP synthase(cGAS),interferon gene stimulator(STING),phosphorylated interferon regulatory factor 3(p-IRF3)and interferon regulatory factor 3(IRF3)in lung tissue of rats.Compared with the CT group,the asthma model group showed obvious pathological damage of bronchial tissue and lung tissue,higher level of airway reactivity,higher pathological scores of lung tissue and bronchial tissue,increased total number of inflammatory cells and the number of monocytes,eosinophils,neutrophils and lymphocytes in BALF,higher levels of inflammatory factors in serum,and higher expression levels of cGAS,STING and p-IRF3/IRF3 proteins in lung tissue(P<0.05).Compared with the M group,the pathological damage of lung and bronchus tissue in asthmatic rats was relieved after treatment with DXMS and high-dose AF,the airway reactivity,pathological score of lung tissue and bronchial tissue,total number and classification of inflammatory cells in BALF,inflammatory factors in serum and expression of cGAS,STING,p-IRF3/IRF3 proteins in lung tissue were obviously lower(P<0.05).In conclusion,AF can alleviate airway inflammation in asthmatic young rats,possibly by inhibiting cGAS-STING signal pathway.
作者
熊甜甜
王锐
谢雄
邹昱琳
XIONG Tiantian;WANG Rui;XIE Xiong;ZOU Yulin(Department of Pediatrics,Gezhouba Central Hospital of Sinopharm,Yichang 443002,China)
出处
《免疫学杂志》
CAS
CSCD
2024年第2期145-150,共6页
Immunological Journal
基金
2021年宜昌市医疗卫生研究项目(A21-2-059)。
作者简介
通信作者:王锐,E-mail:wagmtc@163.com。
