曲古菌素A对脂多糖致急性肺损伤小鼠的保护作用观察  

Protective effects of trichostatin a on lipopolysaccharide-induced acute lung injury in mice

作　　者：雷鸣[1] 倪云峰[1] 李小飞[1] 张志培[1] 刘涛[1] 程庆书[1] 

机构地区：[1]第四军医大学唐都医院胸腔外科,西安710038

出　　处：《解放军医学杂志》2012年第4期283-287,共5页Medical Journal of Chinese People's Liberation Army

摘　　要：目的探讨曲古菌素A(TSA)对脂多糖(LPS)所致急性肺损伤小鼠的保护作用及其机制。方法健康雄性BALB/c小鼠60只,随机分为空白对照组、TSA组(灌胃给予TSA 1mg/kg)、LPS组(气管内给予LPS 1mg/kg)及TSA+LPS组(气管内给予LPS前1h灌胃给予TSA),每组15只。分别于处理后1、3、6、12、24h获取各组小鼠支气管肺泡灌洗液(BALF),采用ELISA法检测其中TNF-α和IL-1β的浓度,并取肺组织测定肺干湿重比,HE染色后行病理组织学观察,ELISA法检测组织匀浆中髓过氧化物酶(MPO)活性及一氧化氮(NO)浓度。结果与空白对照组及TSA组比较,LPS组小鼠肺组织可见明显的炎性细胞浸润等急性肺损伤病理学征象,肺组织湿干重比、MPO活性、NO浓度及BALF中TNF-α、IL-1β浓度均明显升高(P<0.05)。与LPS组比较,TSA+LPS组上述改变均明显受抑,肺组织损伤减轻,组间比较差异有统计学意义(P<0.05)。结论 TSA对LPS诱导的急性肺损伤有保护作用,可能与其抑制了炎性细胞因子的生成有关。Objective To evaluate the protective effect of trichostatin A（TSA） on lipopolysaccharide（LPS）-induced acute lung injury（ALI） in mice,and to explore its mechanism.Methods A total of 60 healthy male BALB/c mice were randomly divided into 4 groups（n=15,each group） as follows： control group,TSA group（TSA 1mg/kg by intragastric administration）,LPS group（LPS 1 mg/kg through trachea）,and TSA＋LPS group（LPS through trachea 1h after TSA by intragastric administration）.The animals in each group were sacrificed at different time points（1,3,6,12,and 24h） after the treatment,and bronchoalveolar lavage fluid（BALF） was obtained from all animals.ELISA method was adopted to detect the concentrations of TNF-α and IL-1β.Dry/wet ratio of lung tissue was measured.The histopathological observation of lung tissue was made after HE staining.ELISA was used to measure the activity of myeloperoxidase（MPO） and the concentration of nitric oxide（NO）.Results Compared with the control and TSA groups,Inflammatory cell infiltration and other pathologic signs of ALI were found in LPS group.The lung wet to dry weight ratio,MPO activity,and concentration of NO in lung tissues,and concentrations of TNF-α and IL-1β in BALF were significantly higher in the LPS group（P0.05）.Compared with the LPS group,the changes in the TSA＋LPS group were significantly less marked.The lung tissue injury was alleviated,and there was statistical significance when compared with LPS group（P0.05）.Conclusions TSA has a protective effect on LPS-induced ALI,and it may be related with its effect on suppression of production inflammatory cytokines.

关 键 词：曲古菌素A 肺损伤 急性 脂多糖类 细胞因子类 

分 类 号：R563.902[医药卫生—呼吸系统]