依达拉奉对脓毒血症大鼠急性肺损伤的保护机制研究

Mechanisms of Protective Effects of Edaravone on Acute Lung Injury in Rats with Sepsis

目的探讨依达拉奉对脓毒血症致急性肺损伤(ALI)的保护机制。方法将60只雄性SD大鼠随机分3组:对照组(NS组)、模型组(LPS组)及依达拉奉治疗组(ED组),每组20只。LPS和ED组采用尾静脉注射LPS(10mg·kg-1)建立ALI模型,ED组随后立即尾静脉注射依达拉奉(5mg·kg-1)。LPS注射6h后抽取动脉血行血气分析测氧分压(PaO2)、二氧化碳分压(PaCO2)、氧合指数(PaO2/FiO2),提取肺组织测定干/湿重比值(D/W),观察肺组织病理改变,测定血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)含量。结果与NS组比较,LPS组肺组织D/W、动脉血气测得PaO2、PaCO2、PaO2/FiO2显著下降,肺损伤病理评分及血浆TNF-α、IL-6升高(P<0.05)。与LPS比较,ED组肺组织D/W、动脉血气测得PaO2、PaCO2、PaO2/FiO2升高,肺损伤病理评分及血浆TNF-α、IL-6明显下降(P<0.05),但仍高于NS组(P<0.05)。结论依达拉奉对急性肺损伤具有保护作用,其机制可能是通过清除肺内氧自由基,减少炎性细胞因子TNF-α、IL-6产生。

Objective To explore the mechanisms of protective effects of edaravone on sepsis-induced acute lung injury（ALI）.Methods Sixty healthy male SD rats were randomly divided into three groups：control group（NS group,n=20）,model group（LPS group,n=20）and edaravone treatment group（ED group,n=20）.ALI was induced by tail vein injection of LPS（10 mg·kg-1 ） in LPS group and ED group.In addition,ED group was given tail vein injection of edaravone（5 mg· kg-1 ）.The arterial blood and lung tissue samples were collected at 6 hours after LPS injection. The oxygen partial pressure（PaO2 ）,carbon dioxide partial pressure（PaCO2 ）and oxygenation in-dex（PaO2/FiO2 ）were measured and the wet/dry（W/D）weight ratio of lung tissue was deter-mined.Furthermore,pathological changes in lung tissue were observed and tumor necrosis factor （TNF-α）and interleukin-6 （IL-6）levels in plasma were detected.Results Compared with NS group,W/D lung weight ratio,PaO2 ,PaCO2 and PaO2/FiO2 decreased in LPS group（P 〈0.05）, and pathological scores and plasma TNF-α and IL-6 levels increased in both LPS group and NS group（P 〈0.05）.Compared with LPS group,W/D lung weight ratio,PaO2 ,PaCO2 and PaO2/FiO2 increased and pathological scores and plasma TNF-αand IL-6 levels decreased in LPS group （P 〈0.05）.Conclusion Edaravone exerts protective effects on ALI,and the mechanisms of ac-tion may be mediated by scavenging free radicals and reducing the production of TNF-a and IL-6.