依达拉奉对大鼠急性肺损伤的干预作用

目的 探讨依达拉奉(EDA)和地塞米松(DXM)对脓毒症大鼠肺损伤的干预作用.方法 50只SD大鼠随机分为假手术组(sham组)、手术对照组(CLP组)、依达拉奉治疗组(EDA组)、地塞米松治疗组(DXM组)和依达拉奉联合地塞米松治疗组(E+D组).采用盲肠结扎穿刺法造脓毒血症大鼠肺损伤模型,药物治疗组造模后立即经阴茎背静脉注射EDA(5mg/kg),DXM(5mg/kg)或EDA(5mg/kg)+DXM(5mg/kg);另两组均以等量生理盐水代替.结果 与 sham组相比,CLP组大鼠病理评分,肺干湿重比(W/D),肺泡通透指数(LPI),肺组织中MPO,MDA,IL-6,TNF-α,肺组织中凋亡细胞数量明显增加,而肺组织中T-AOC活性明显减轻.应用地塞米松,依达拉奉药物干预后,上述指标均有不同程度的改善.两种药物联合应用与单个药物应用相比,这些指标有更明显的改善.结论 依达拉奉预处理对脓毒症诱导的肺损伤有明显的防治效果,减轻急性肺损伤的机制可能是通过减少氧自由基产物,减少炎性细胞因子浓度.依达拉奉和地塞米松联合应用对肺损伤有更好的治疗效果.

The effect of pretreatment with edaravone on sepsis induced acute lung injury in rats

Objective Based on the known properties of edaravone(EDA) and dexamethasone (DXM) to inhibit inflammation and oxidative stress,the present study was designed to investigate potential effects of EDA and DXM on acute lung injury induced by cecum ligation and puncture (CLP) in rats. Methods Acute lung injury following sepsis was reproduced by cecum ligation and puncture (CLP) in fifty male Sprague-Dawley(SD) rats. The experiments were randomized into 5 groups (each group n = 10):sham group,CLP group, edaravone group( EDA group, EDA 5 mg/kg), dexamethasone group( DXM group, DXM S mg/kg), edaravone and dexamethasone group(E + D group, EDA S mg/kg + DXM 5 mg/kg) EDA or/and DXM was administrated after CLP via single vena dorsalis penis injection. Other two groups were given the same volume of saline following CLP. Results In vivo,acute lung injury resulted from sepsis was characterized by an increase in lung injury score, lung microvascular permeability, serum malondialdehyde ( MDA) and the level of myeloperoxidase( MPO) activity, tumor necrosis factor-a, interleukin-6 and MDA in the lung tissue, accompanied with a decrease in total anti-oxidative capability (T-AOC) in the serum and lung tissue ampared with the sham group,the above biomarkers were improved by using EDA or DXM. Conclusion Pretreatment with EDA has protective effects on lung injury resulted from spesis. EDA attenuates acute lung injury likely by means of minimizing oxidative stress and inhibiting expression of proinflammatory cytokines. The combined use of EDA and DXM may be more beneficial than the use of a single agent.