内毒素致急性肺损伤大鼠肺组织信号转导和转录激活因子1的调控作用

Regulatory effect of signal transducer and activator of transcription 1 on acute lung injury induced by endotoxin in rat

目的探讨信号转导和转录激活因子1（STAT1）在内毒素致急性肺损伤（ALI）大鼠肺组织中的表达及其调控作用。方法静脉注射内毒素脂多糖（LPS）制备大鼠ALI模型。将动物随机分为对照组、LPS组、地塞米松（DEX）干预组；DEX干预组灌胃DEX0．135mg／kg，对照组和LPS组分别灌胃等量生理盐水，连用5d后LPS组和DEX干预组经尾静脉注射LPS5mg／kg，对照组以生理盐水1ml替代。于致伤后1、2、4、8、16h各处死6只大鼠，取肺组织，用蛋白质免疫印迹法（Western blotting）测定STAT1表达的动态变化，光镜下观察肺组织病理学改变。结果与对照组比较，LPS组STAT1的活化从1h开始增高，4h达高峰，然后逐渐下降；2、4、8h时STATl表达显著升高（P均d0．01）；DEX干预组STATl表达趋势同LPS组，但2、4、8h时STAT1表达显著低于LPS组（P均〈0．05）。结论内毒素致AL1中存在STAT1异常表达；STAT1参与了肺组织炎症的形成。

Objective To investigate the expression and regulatory effect of signal transducer and activator of transcription 1 （STAT1） in acute lung injury （ALI） induced by endotoxin. Methods ALI model was induced by intravenous lipopolysaccharide （LPS）. Wistar rats were randomly divided into three groups, the control group, LPS group, dexamethasone （DEX） group. Each group was subdivided into five subgroups according to the time after administration of endotoxin （1, 2, 4, 8 and 16 hours）, except the control group. Rats were given normal saline by gavage in control group and LPS group, and 0. 135 mg/kg DEX in DEX group for 5 days. Six rats were sacrificed at different time points after normal saline or LPS injection. The lungs were harvested for microscopic examination. Western blotting was used to examine protein expression of STAT1 in lung tissue. Results In LPS group the levels of STAT1 began to increase at 1 hour, reaching the peak value at 4 hours, then declined gradually. There was a significant difference at 2, 4, 8 hours （all P〈0. 01）. The expression trend for STAT1 was similar between DEX and LPS groups, but the levels of STAT1 were significantly decreased in DEX group at 2, 4, 8 hours compared with the LPS group （all P〈0. 05）. Conclusion There is abnormal expression of STAT1 in the lung tissue of ALI. The abnormal STAT1 expression takes part in the inflammatory formation of lung tissue in ALI.