乙酰化白藜芦醇对脂多糖诱导急性肺损伤中微循环修复作用机制探究  

3,5,4′-Tri-O-acetylresveratrol alleviates lipopolysaccharide-induced acute lung injury by regulating lung microcirculation

作　　者：闫雪[1] 崔蕊[1] 熊晓毅[1] 张敏龙 Yan Xue;Cui Rui;Xiong Xiaoyi;Zhang Minlong(School of Medicine,Xianyang Vocational Technical College,Xianyang 712000,China;Department of Respiratory Medicine,Tangdu Hospital,the Fourth Military Medical University,Xi′an 710038,China)

机构地区：[1]咸阳职业技术学院医学院,712000 [2]空军军医大学唐都医院呼吸科,西安710038

出　　处：《国际呼吸杂志》2021年第6期410-415,共6页International Journal of Respiration

基　　金：咸阳职业技术学院重大科学研究项目(2019KYA02)。

摘　　要：目的观察脂多糖(LPS)诱导急性肺损伤大鼠肺组织中微循环的变化,探讨乙酰化白藜芦醇对其干预作用及机制。方法 32只SD大鼠随机分为空白对照组、LPS处理组、乙酰化白藜芦醇预处理组和白藜芦醇预处理组,每组8只。采用气管内滴注LPS(5 mg/kg)的方法制作急性肺损伤动物模型,观察病理变化、肺组织湿/干重比值,用伊文思蓝法检测肺微血管通透性,用酶联免疫吸附试验法检测肺组织中肿瘤坏死因子α和白细胞介素1β的含量,用蛋白质印迹法检测细胞骨架重构相关蛋白FAK、cofilin的表达变化,免疫荧光观察肺微血管内皮细胞单层细胞间隙改变情况。结果 LPS干预4 h后,大鼠肺部损伤明显,肿瘤坏死因子α和白细胞介素1β的含量增高,肺湿/干重比值及通透性明显增加,FAK-cofilin通路明显激活,肺微血管内皮单层细胞间隙明显增加;乙酰化白藜芦醇预处理显著减轻了LPS导致的急性肺损伤,减少了炎症因子的释放,并且抑制了FAK-cofilin通路的激活及肺微血管内皮单层细胞间隙的增加。结论肺微循环的改变参与了LPS诱导肺损伤的发生发展,乙酰化白藜芦醇能够通过抑制FAK-cofilin通路减轻肺损伤。Objective To observe the change of lung microcirculation in lipopolysaccharide(LPS)-induced acute lung injury,and explore the intervention effect and the mechanism of 3,5,4′-Tri-O-acetylresveratrol.Methods Thirty-two rats were randomly divided into four groups:normal control group,LPS group,3,5,4′-Tri-O-acetylresveratrol pre-treated group and acetylresveratrol pre-treated group,eight rats in each group.The acute lung injury animal model was made by 5 mg/kg LPS instillation into the airway.The pathological changes,wet/dry weight ratio of lung tissues were observed.Evans blue method was used to detect pulmonary microvascular permeability.Enzyme-linked immunosorbent assay was used to detect the levels of tumor necrosis factor-αand interleukin-1βin lung tissues.Western blot was used to detect the expressions of FAK and cofilin.The immunofluorescence was used to observe the changes of monolayer permeability of pulmonary microvascular endothelial cells.Results After LPS stimulation for four hours,the lung injury of rats was obvious,the levels of tumor necrosis factor-αand interleukin-1βwere increased,the wet/dry weight ratio and permeability of lung tissues were increased,FAK-cofilin pathway was activated,and the monolayer permeability of pulmonary microvascular endothelial cells was increased.Pretreatment with 3,5,4′-Tri-O-acetylresveratrol significantly attenuated LPS-induced acute lung injury,reduced the release of inflammatory factors,and inhibited the activation of FAK-cofilin pathway and the increase of monolayer permeability of pulmonary microvascular endothelial cells.Conclusions The changes of lung microcirculation are involved in the occurrence and development of LPS-induced lung injury.3,5,4′-Tri-O-acetylresveratrol can reduce lung injury by inhibiting FAK-cofilin pathway.

关 键 词：急性肺损伤 脂多糖类 FAK-cofilin通路 微循环 乙酰化白藜芦醇 

分 类 号：R285.5[医药卫生—中药学]