水飞蓟宾对哮喘小鼠气道黏蛋白Muc5ac的影响及机制研究  

Effects of silybin on airway Muc5ac in asthmatic mice and its mechanisms

作　　者：刘婷婷 黄志豪 杨红霞 张建勇 Liu Tingting;Huang Zhihao;Yang Hongxia;Zhang Jianyong(Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China;Department of Infectious Diseases,Zigong First People’s Hospital,Zigong Sichuan 683000,China)

机构地区：[1]遵义医科大学附属医院呼吸与危重症医学科,贵州遵义563099 [2]四川省自贡市第一人民医院感染科,四川自贡683000

出　　处：《遵义医科大学学报》2024年第2期121-126,共6页Journal of Zunyi Medical University

基　　金：贵州省中医药管理局中医药、民族医药科学技术研究课题(NO:QZYY-2020-060);遵义市科技厅项目[NO:遵市科合HZ字(2021)24]。

摘　　要：目的观察水飞蓟宾对哮喘小鼠气道黏蛋白Muc5ac表达水平的影响,并探讨其可能作用机制。方法40只SPF级雌性BALB/c小鼠随机分为正常组(NS组)、哮喘组(AS组)、水飞蓟宾40 mg/kg组(Silybin40组)、水飞蓟宾80 mg/kg组(Silybin80组)、地塞米松组(DEX组)。通过OVA致敏和雾化激发制备哮喘小鼠模型。AS组、Silybin40组、Silybin80组及DEX组分别以PBS、水飞蓟宾40 mg/kg、水飞蓟宾80 mg/kg及地塞米松2 mg/kg干预。收集各组小鼠BALF,分别行细胞总数计数、嗜酸性粒细胞百分比,ELISA法检测IL-6及TNF-α水平;制备肺组织病理石蜡切片,行HE、AB-PAS观察肺组织病理学改变,IHC检测肺组织ERK、pERK、SP1、Muc5ac蛋白表达水平。结果AS组小鼠BALF细胞总数、嗜酸性粒细胞百分比、IL-6、TNF-α、气道周围炎症细胞浸润评分、气道黏液物质相对着色面积、肺组织pERK、SP1及Muc5ac蛋白水平均高于NS组(P<0.05),Silybin80组和Silybin40组BALF细胞总数、嗜酸性粒细胞百分比、IL-6、TNF-α、气道周围炎症细胞浸润评分、气道黏液物质相对着色面积、肺组织pERK、SP1及Muc5ac蛋白水平均低于AS组(P<0.05),且Silybin80组上述指标的水平均低于Silybin40组。结论水飞蓟宾干预可抑制哮喘小鼠气道炎症和气道黏液高分泌,其机制可能与抑制ERK/SP1信号通路有关。Objective To observe the effects of silybin on the expression levels of airway mucin Muc5ac in asthmatic mice,and to explore its possible mechanism.Methods Forty SPF-grade female BALB/c mice were randomly divided into the control group(NS group),Asthma model group(AS group),Silybin 40 mg/kg group(Silybin40 group),Silybin 80 mg/kg group(Silybin80 group)and Dexamethasone group(DEX group).Asthmatic models were established by OVA sensitization and aerosolization challenges in mice.The AS group,Silybin40 group,Silybin80 group,and DEX group were treated with PBS,Silybin 40 mg/kg,Silybin 80 mg/kg and Dexamethasone 2 mg/kg respectively.The BALF of mice in each group was collected for detection of total cell count and the percentage of eosinophils,and the levels of IL-6 and TNF-αwere measured by ELISA.The lung tissues were prepared into paraffin-embedded sections,which were then subject to HE staining and AB-PAS staining to observe the pathological changes of lung tissues.Immunohistochemistry was used to detect the protein expression levels of ERK,pERK,SP1,and Muc5ac in lung tissues.Results The total number of BALF cells,the percentage of eosinophils,the levels of IL-6 and TNF-αin BALF,the infiltration scores of inflammatory cells around the airway,the area of airway mucus,and the protein levels of pERK,SP1 and Muc5ac in lung tissue in the AS group were higher than those in the NS group(P<0.05).The total number of BALF cells,the percentage of eosinophils,the levels of IL-6 and TNF-αin BALF,the infiltration scores of inflammatory cells around the airway,the area of airway mucus,and the protein levels of pERK,SP1,and Muc5ac in lung tissue in the Silybin80 group and Silybin40 group were lower than those in the AS group(P<0.05),and the levels of the above indexes in the Silybin80 group were lower than those in the Silybin40 group.Conclusion Silybin can inhibit airway inflammation and airway mucus hypersecretion in asthmatic mice,which may be related to the inhibition of the ERK/SP1 signaling pathway.

关 键 词：哮喘 水飞蓟宾 气道炎症 Muc5ac蛋白 

分 类 号：R562[医药卫生—呼吸系统]