乌司他丁对急性肺损伤大鼠肺组织高迁移率族蛋白B1表达的影响

Effect of Ulinastatin on the Expression of HMGB1 in Rats with Acute Lung Injury

【目的】探讨乌司他丁对急性肺损伤（acute lung injury，ALI）大鼠肺组织高迁移率族蛋白B1（HMGBl）表达的影响。【方法】采用腹腔注射脂多糖（LPS）制备Au动物模型。90只雄性SD大鼠，随机分为正常对照组（n=10）、ALI组（n=40）和乌司他丁（Ulinastatin，UTI）干预组（UTI组，n=40），建模后6h、12h、24h、48h处死，光镜观察肺组织病理变化，检测肺含水分数、动脉血气分析，采用实时荧光定量聚合酶链反应（tealtime-PCR）法检测肺组织HMGB1mRNA的表达水平，酶联免疫吸附法（ELISA）检测肺组织匀浆中HMGB1表达水平。【结果】与正常对照组比较，ALI组大鼠肺组织呈局灶性肺不张及肺水肿表现，伴有炎性细胞浸润，肺含水分数明显增加，PaO2进行性下降，肺组织HMGB1表达水平均升高；与ALI组相比较，UTI组肺组织炎症减轻，肺含水分数下降，PaO2明显上升，肺组织HMGB1表达水平明显下降。【结论】乌司他丁能够下调肺组织HMGB1表达，减轻脂多糖诱导的ALI。

[Objective]To investigate the effect of Ulinastatin on the expression of High-Mobility Group Protein B1 （HMGB1）over the course of acute lung injury induced by Lipopolysaccharide endotoxin in rats. [Methods]LPS（5 mg/kg,ip）-induced acute lung injury model was used in our experiment. 90 healthy, Spra- gue-Dawley male rats were randomly divided into three groups： a control group （C group, n = 10）, an acute lung injury group （ALl group, n =40）, and a ulinastatin intervention group （UTI group, n =40）. Rats were sacrificed separately 6 h, 12 h, 24 h, and 48h after the injection. The pathology of lung tissue was evaluated by staining HE, measuring wet-to-dry （W/D） weight ratio of lung, analyzing arterial blood PaO2, detecting mR- NA expression of lung tissue by real time- PCR, and detecting HMGB1 concentration in lung homogenate u- sing ELISA.[Results]Compared to the C group, the pathological changes in the lung of rats in the ALI group showed focal ate[ectasis and pulmonary edema and inflammatory cell infiltration. Lung W/D weight ratio were higher, while PaO2 levels were significantly lower. The expression levels of HMGB1 were significantly higher. Compared to the ALI group, the rate of inflammatory changes and lung W/D weight ratio in the lung of rats in the UTI group were significantly lower, while PaO2 levels were significantly higher. The expression levels of HMGB1 were significantly lower. [Conclusion] UTI could down-regulate HMGB1 expression in lung tissue and attenuate LPS-induced acute lung injury.