目的探讨自由基清除剂依达拉奉对机械通气所致急性肺损伤的保护作用。方法清洁级雄性SD大鼠24只,随机分为3组(n=8),常规潮气量组(C组),大潮气量组(MV组),大潮气量+依达拉奉组(E组)。C组行常规潮气量(VT=8 mL/kg)机械通气4 h,其余两组均行大潮气量(VT=40 mL/kg)机械通气4 h。E组于机械通气前30 min经股静脉注射0.2%的依达拉奉15 mg/kg,C组和MV组于机械通气前30 min经股静脉注射等量的生理盐水。机械通气4 h后留取肺标本,分别测定肺组织湿/干重比值(W/D)和肺组织匀浆中髓过氧化物酶(MPO)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量,观察肺组织病理改变及肺组织核因子κB(NF-κB)表达情况。结果 MV组肺组织MPO、MDA含量、W/D及肺组织NF-κB表达均高于C组(P〈0.05),肺组织SOD含量低于C组(P〈0.05)。E组肺组织MPO、MDA含量、W/D及肺组织NF-κB表达均低于MV组,仍高于C组(P〈0.05);E组肺组织SOD含量高于MV组,仍低于C组(P〈0.05)。结论依达拉奉可以减轻机械通气所致的大鼠急性肺损伤,其机制可能与清除活性氧族(ROS),降低了NF-κB信号转导通路的活化,进而减轻炎症级联放大效应有关。
Objective To explore the potential protective effect in vivo of Edaravone,a free radical scavenger,on me chanical ventilation-induced lung injury in rats.Methods 24 healthy male SD rats weighing 280-320 g were randomly divided into 3 groups(n =8): traditional tidal volume group(group C),large tidal volume mechanical ventilation group(group MV) and Edaravone pretreatment group(group E).In group C rats were ventilated with traditional tidal volume(VT=8 mL/kg) for 4 h.In group MV and E the animals were mechanically ventilated with high volume ventila tion(VT=40 mL/kg) for 4 h.In group E 0.2% Edaravone 15 mg/kg was administered iv at 30 min before mechanical ventilation.Equal amount of normal saline was given to rats in other two groups at the same time.The lung tissue samples were collected at 4 h after mechanical ventilation.The wet/dry(W/D) weight ratio of lung tissue was mea sured.The levels of myeloperoxidase(MPO),malondialdehyde(MDA) and superoxide dismutase(SOD) in lung tissue homogenate were assayed.The pathological changes and expression of nuclear factor-kappa B(NF-κB) in lung tissue were also studied.Results Compared with the C group,the W/D,NF-κB expression,MPO and MDA levels in the MV group were significantly higher(all P 0.05),and the level of SOD was apparently lower(P 0.05).The W/D,NF-κB expression,MPO and MDA levels in the E group were significantly lower than those in the MV group(all P 0.05),and higher than those in the C group(all P 0.05).And the level of SOD in lung tissue of the E group was higher than that in the MV group and lower than that in the C group(P 0.05).Conclusion Edaravone has protective effect on mechanical ventilation-induced lung injury in rats.The mechanism maybe related to its ability of clearing the reac tive oxygen species,inhibiting the activation of the signal pathway of NF-κB and inflammatory cascade.