秦皮甲素对LPS诱导小鼠急性肺损伤的作用及机制研究

Effect of esculin on acute lung injury induced by LPS in mice and possible mechanism

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.