摘要
目的:研究秦皮甲素对脂多糖(LPS)诱导的小鼠急性肺损伤的保护作用及其机制。方法:BALB/c小鼠随机分组:正常对照组、LPS模型组、秦皮甲素25,50和100 mg·kg-1给药组。连续给秦皮甲素7 d,于末次给药后腹腔注射(ip)LPS 5 mg·kg-1建立小鼠肺损伤模型,6 h后取材检测。HE染色观察肺组织形态;ELISA法检测肺组织中炎症因子及黏附分子;Western Blot法检测炎症通路相关蛋白的表达。结果:与正常对照组比较,小鼠ip LPS可诱导肺泡毛细血管充血及肺泡壁增厚,出现肺部炎症反应,炎症因子及黏附分子IL-1β,IL-6,TNFα,MCP-1,ICAM-1显著增高,炎症通路蛋白HMGB1,TLR4表达显著增加;而秦皮甲素25,50和100 mg·kg-1给药处理可显著改善LPS诱导的肺组织损伤,降低LPS诱导的炎症因子及黏附分子水平,抑制炎症通路蛋白HMGB1,TLR4蛋白的表达。结论:秦皮甲素可改善LPS诱导的小鼠急性肺损伤及炎症反应,其机制可能与其下调HMGB1/TLR4炎症通路相关。
Objective: To investigate the effects of esculin on acute lung injuries induced by lipopolysaccharide( LPS) and explore its anti-inflammatory mechanism in mice. Methods: BALB/c mice were randomly divided into the following groups: normal control group,LPS model group,esculin 25,50,and 100 mg·kg^-1 treatment group.Pretreatment with esculin at dose of 25,50,and 100 mg·kg^-1 individually for 7 days,the model of lung injury in mice was established by intraperitoneal injection of LPS 5 mg·kg^-1 on the 7 thday. After administration of LPS for6 h,the samples were taken for detection. The lung histological morphology was analyzed after HE staining. The levels of inflammatory factors and adhesion molecules in lung tissues by ELISA assay. Inflammatory pathway proteins including HMGB1 and TLR4 were analyzed by Western Blot. Results: Compared with the normal control,LPS induced alveolar capillary hyperemia,alveolar wall thickening,and release of inflammatory factors and adhesion molecules. In addition,both the inflammatory pathway proteins HMGB1 and TLR4 were significantly increased.However,treatment with esculin 25,50 and 100 mg·kg^-1 reduced lung injury induced by LPS,decreased release of inflammatory factors and adhesion molecule including IL-1β,IL-6,TNFα,MCP-1 and ICAM-1,and inhibited the expression of inflammatory proteins including HMGB1 and TLR4. Conclusion: Esculin can improve the acute lung injury and inflammation induced by LPS in mice,and its anti-inflammation mechanism may be related to downregulationof HMGB1/TLR4 inflammatory pathway.
作者
程笑
杨滢霖
李伟瀚
王月华
杜冠华
CHENG Xiao;YANG Ying-lin;LI Wei-han;WANG Yue-hua;DU Guan-hua(Beijing Key Laboratory of Drug Target Identification and New Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2018年第16期1849-1854,共6页
Chinese Journal of New Drugs
基金
国家"重大新药创制"科技重大专项资助项目(2012ZX09103101-078
2018ZX09711001-003-019)
国家自然科学基金面上项目(81473383)
中国医学科学院医学与健康科技创新工程(2016-I2M-3-007)
北京协和医学院博士创新基金(2017-1007-02)
关键词
秦皮甲素
脂多糖
急性肺损伤
炎症反应
esculin
lipopolysaccharide
acute lung injury
inflammation