目的探讨不同剂量地塞米松对兔海水淹溺性肺水肿(pulm onary edem a of seaw ater drow ning,PE-SW D)的治疗作用及其机制。方法 40只家兔随机分为4组:对照组(C G)、海水淹溺组(SG)和不同剂量地塞米松治疗组(D G 1:0.2 m g/kg,D G 2:1 m g/kg)。SG组兔给予气管内灌注3 m L/kg海水,D G 1及D G 2组在C G组的基础上分别静注0.2 m g/kg、1 m g/kg地塞米松。于淹溺前及淹溺后30 m in,120 m in进行动脉血气分析,淹溺后120 m in采血、收集肺泡灌洗液并取肺组织,测定肺湿/干重比、肺泡灌洗液蛋白含量,以生化法测定血清一氧化氮(N O)、丙二醛(M D A)、总超氧化物歧化酶(T-SO D)含量,观察肺组织病理形态并计算肺损伤病理评分。结果与C G组比较,SG、D G 1、D G 2组在淹溺后30 m in PaO 2显著下降(P〈0.01),但在淹溺后120 m in,D G 1及D G 2组较SG组PaO 2明显增高(P〈0.05);在淹溺后120 m in,D G 1及D G 2组较SG组肺湿/干重比、肺泡灌洗液蛋白含量及肺损伤病理评分显著下降(P〈0.05),但D G 1组与D G 2组之间比较无明显差异(P〉0.05);与C G组比较,SG组血清N O 2-/N O 3-和M D A含量显著增高(P〈0.01),SO D含量显著下降(P〈0.01),但D G 1及D G 2组与SG组比较,N O 2-/N O 3-和M D A含量明显下降(P〈0.05),SO D含量明显增高(P〈0.05),但两组之间差异无显著性(P〉0.05)。结论地塞米松可改善兔海水淹溺性肺水肿的缺氧、减轻肺损伤程度,但增加剂量并不能增加治疗效果,其作用机制复杂,部分与提高血清抗氧自由基水平,抑制脂质过氧化反应有关。
【Objective】 To observe the therapeutic effect of Dexamethasone with different doses on rabbits with pulmonary edema induced by seawater drowning and explore the possible mechanisms.【Methods】 40 rabbits were randomly divided into 4 groups: control group(CG),seawater drowning group(SG),Dexamethasone group(0.2 mg/kg as DG1,1.0 mg/kg as DG2),with 10 in each group.Seawater(3 mg/kg body weight) was instilled into the lower trachea of rabbits in SG,DG1 and DG2.These rabbits were assigned randomly to receive injection of 2 mL of saline(SG) or 0.2 mg/kg(DG1),1 mg/kg(DG2) body weight of Dexamethasone.Arterial blood gas analysis was performed before seawater drowning and 30 min,120 min after seawater drowning.The lung samples and bronchial alveolar lavage fluid(BALF) were collected for detecting the ratio of lung wet/dry weight,protein content in BALF and lung injury scores.The levels of nitric oxide(NO),malondialdehyde(MDA),and superoxide dismutase(SOD) in blood serum were evaluated by biochemical methods.【Results】 Compared with CG,the PaO2 in SG,DG1 and DG2 decreased significantly(P 0.01) 30 min after seawater drowning,while the PaO2 in DG1 and DG2 increased significantly(P 0.05) 120 min after seawater drowning compared with SG.Compared with SG,the ratio of lung wet/dry weight,protein content in BALF and lung injury scores in DG1 and DG2 decreased(P 0.05),while there was no significant difference between DG1 and DG2(P 0.05).Compared with CG,the level of NO2-/ NO3-and MDA increased significantly(P 0.05),while the level of SOD decreased in DG1 and DG2(P 0.05).【Conclusions】 Dexamethasone could improve hypoxia of PE-SWD in rabbits and attenuate lung injury in a dose-independent manner,which might be partly associated with the enhanced inhibition of lipid peroxidation by incremental serum antioxidase.