依布硒啉对大鼠脂多糖诱导的急性肺损伤的保护作用

目的探讨依布硒啉对内毒素性急性肺损伤大鼠肺功能的保护作用及对肺组织中相关细胞因子表达的影响。方法健康雄性SD大鼠随机分成6组：正常对照组,模型组,地塞米松对照组,依布硒啉30、15和7.5 mg/kg治疗组。通过大鼠尾静脉注射脂多糖（5 mg/kg）建立急性肺损伤模型,治疗大鼠组于造模前30 min腹腔注射给药,对照组和模型组分别注入等量溶剂。造模后6 h,麻醉抽取动脉血并放血处死动物,检测动脉血氧分压（PaO2）和二氧化碳分压（PaCO2）,取肺组织,测定肺湿/干质量比,收集支气管肺泡灌洗液,检测其中总蛋白水平。分别检测肺组织中丙二醛（MDA）、TNF-α含量及核因子E2相关因子（Nrf2）蛋白表达。结果与模型组相比,依布硒啉15和30 mg/kg剂量组大鼠动脉血中PaO2明显增高、PaCO2明显降低,肺湿/干质量比降低,肺组织MDA和TNF-α含量显著减少,而Nrf2表达明显增高。结论依布硒啉对内毒素性急性肺损伤有一定保护作用,其机制可能与诱导Nrf2表达有关。

Protetive effect of ebselen on lipopolysaccharide-induced acute lung injury in rats

Objective To investigate the protective effect of ebselen on lung function and effect on relative cytokine expression in lung tissue of rat with endotoxin-induced acute lung injury.Methods Healthy male SD rats were randomly divided into six groups：normal control group,model group,ebselen 30,15 and 7.5 mg/kg treatment groups,and dexamethasone treatment group.Model was established by intravenous injection of lipopolysaccharide（5 mg/kg）.Rats in ebselen treatment group were intraperitoneally injected with ebselen（7.5,15 and 30 mg/kg） at 30 minutes before modeling.Rats in dexamethasone group were intraperitoneally injected with dexamethasone（5 mg/kg）,rats in normal control group and model group were injected with the same amount of solvent.Six hours later,the animals were anesthetized and sacrificed by bleeding.The arterial blood was collected and the partial pressure of oxygen（PaO2） and carbon dioxide（PaCO2） was detected.The bronchoalveolar lavage fluid（BALF） was collected to detect the level of protein.The lung tissues were collected to detect wet/dry weight ratio（W/D） and the levels of malondialdehyde（MDA）,TNF-α and nuclear factor erythroid 2-related factor（Nrf2）.Results Compared with model group,the protein in BALF and the W/D of lung tissues in ebselen treatment group were significantly reduced;the levels of MDA,TNF-α and Nrf2 in lung tissue were significantly decreased,and the pathology improved significantly.Conclusion Ebselen has a protective effect on endotoxin induced acute lung injury and its mechanism may be related with the inducing of the expression of Nrf2.