地塞米松通过加强自噬和抑制凋亡减轻海水吸入型肺损伤  

Dexamethasone alleviates seawater aspiration-induced acute lung injury by enhancing autophagy and inhibiting apoptosis

作　　者：王莉[1] 张敏龙[1] 金发光[1] 

机构地区：[1]第四军医大学唐都医院呼吸内科,西安710032

出　　处：《中华肺部疾病杂志（电子版）》2014年第6期15-18,共4页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：国家自然科学基金(81270124)

摘　　要：目的探讨海水吸入型肺损伤中自噬过程,以及地塞米松对其干预作用。方法 40只大鼠完全随机分为正常对照组、1、3、6、12 h海水处理组,每组8只。采用气管内滴注海水(3 ml/kg)的方法制作海水吸入型急性肺损伤大鼠模型,观察病理变化,检测肺组织湿干比,western blot检测beclin-1的表达变化。体外实验A549细胞分为正常对照组、12 h海水组、地塞米松+12 h海水组、3-MA+12 h海水组,采用western blot检测beclin-1和bax的表达变化。结果海水吸入后,大鼠肺部严重损伤,水肿明显,beclin-1随损伤时间延长表达量增加,在海水处理后12 h达到高峰。体外实验中海水刺激增加了beclin-1和bax的表达,然而与海水组相比,地塞米松预处理增加了beclin-1的表达,同时使bax的表达下降。3-MA预处理则效果相反。结论自噬参与了海水吸入型肺损伤的修复过程,地塞米松能够通过加强自噬并且抑制凋亡减轻肺损伤。Objective To observe the process of autophagy in seawater aspiration-induced acute lung injury and the intervention effect of dexamethasone.Methods 40 rats were randomly divided into 5 groups：normal control group,1 h,3 h,6 h,and 12 h seawater group.Every group contains 8 rats.Seawater aspiration-induced acute lung injury model was made by seawater instillation （3 ml/kg） into the airway.Pathological changes and lungs＇wet/dry ratio were carried out after modeling.The expression of beclin-1 was measured by western blot.A549 cells were divided into 4 groups：normal control group,12 h seawater group,dexamethasone ＋ 12 h seawater group,3-MA ＋ 12 h seawater group.The expression of beclin-1 and bax was measured by western blot.Results After seawater stimulation,manifestations of lung injury and edema were obvious.The expression of beclin-1 was up-regulated along with the extension of time and reached the peak at 12 h after seawater aspiration.In cells experiment,seawater stimulation increased the expression of beclin-1 and bax.However,pre-treatment of dexamethasone increased the expression of beclin-1 and attenuated the expression of bax compared with seawater group.Furthermore,3-MA had an opposite effect with dexamethasone.Conclusion Autophagy plays an important part in the repairmen of seawater aspirationinduced acute lung injury.Dexamethasone attenuated lung injury by enhancing autophagy and inhibiting apoptosis.

关 键 词：急性肺损伤 海水 地塞米松 自噬 细胞凋亡 

分 类 号：R563[医药卫生—呼吸系统]