藤黄酸减轻脂多糖诱导的小鼠急性肺损伤

Gambogic acid attenuates lipopolysaccharide-induced acute lung injury in mice

目的探讨藤黄酸(GA)对脂多糖(LPS)所致小鼠急性肺损伤的保护作用及其机制。方法采用尾静脉注射LPS(4 mg/kg)建立小鼠急性肺损伤模型。实验将小鼠随机分为对照组(control组)、模型组(model组)、藤黄酸组(GA组)和藤黄酸预处理组(GA+LPS组),6 h后测定肺湿/干重比值(W/D);检测髓过氧化物酶(MPO)活性;检测肺泡灌洗液(BALF)中蛋白含量和白细胞计数;ELISA检测肺匀浆中白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量。结果模型组小鼠肺W/D、MPO活性、BALF中蛋白含量和白细胞数量均增加,肺组织IL-1β和TNF-α水平升高(均P<0.01);藤黄酸预处理可减轻LPS引起的以上指标变化(均P<0.05)。结论 GA可减轻LPS诱导的急性肺损伤,其机制可能与降低肺组织IL-1β和TNF-α的含量、抑制中性粒细胞在肺部的聚集和减轻肺部水肿相关。

Objective To explore the effects and mechanism of gambogic acid（ GA） on lipopolysaccharide（ LPS）-induced acute lung injury（ ALI）. Methods ALI model was established by the injection of lipopolysaccharide into the tail vein of mice（ 4 mg/kg,iv）. The mice were randomly divided into control group（ control）,model group（ model）,GA group（ GA）,and pretreatment with GA of ALI group（ GA＋LPS）. After six hours,the wet/dry weight ratio（ W/D） of the lung,myeloperoxidase（ MPO） activity in lung tissue,total proteins and number of white blood cells in bronchoalveolar lavage fluid（ BALF） were determined. Tumor necrosis factor-α（ TNF-α） and interleukin-1β（ IL-1β） were measured by the enzyme-linked immunosorbent assay methods. Results Compared with control group,the wet/dry weight ratio（ W/D） of the lung,MPO activity in lung tissue,levels of total proteins and number of white blood cells in BALF of LPS group obviously increased,in addition the level of lung tissue TNF-α and IL-1β in LPS group were significantly higher（ all P〈0. 01）,while in GA pretreatment groups alleviated all the changes in ALI mice. Conclusions GA pre-treatment attenuated LPS-induced ALI,possibly by inhibiting inflammatory cytokines production so as to decrease the recruitment of neutrophils,reduce pulmonary edema.