氨基胍对大鼠内毒素性肺损伤的影响  

Effects of aminoguanidine on endotoxin-induced pulmonary injury in rats

作　　者：张建新[1] 李立萍[1] 李兰芳[1] 董淑婷[2] 李国风[1] 卢安[1] 

机构地区：[1]河北省医学科学院,石家庄市050021 [2]石家庄市第三医院

出　　处：《中华麻醉学杂志》2003年第8期603-607,共5页Chinese Journal of Anesthesiology

基　　金：国家人事部回国留学人员重点资助项目(9900789);河北省博士基金资助项目(99547015D)

摘　　要：目的 观察诱导型一氧化氮合酶抑制剂氨基胍(AG)对内毒素性肺损伤的影响。方法采用静脉注射脂多糖(LPS)制备内毒素性肺损伤大鼠模型。将40只SD雄性大鼠随机分为5组:空白对照组、LPS组、AG高剂量(100 mg/kg)、中剂量(50mg/kg)、低剂量(25 mg/kg)治疗组,LPS组、AG高剂量、中剂量和低剂量治疗组手术后稳定1 h静脉注射LPS(5 mg/kg),空白对照组给等量生理盐水,AG高剂量、中剂量和低剂量治疗组于给予LPS 3 h后经腹腔给AG,空白对照组和LPS组给等量生理盐水。实验过程中监测平均动脉压(MAP),于注射LPS后1、3和6 h时取静脉血0.4 ml测定血浆NO浓度,于注射LPS 6 h后处死大鼠,迅速取出肺脏,测定肺系数、肺含水量和肺组织中丙二醛(MDA)含量、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)活性的变化;在光镜下观察肺形态结构的变化。结果LPS可明显降低MAP,升高肺系数和肺含水量,升高血浆中NO含量,可显著升高肺组织中NOS活性、增加MDA含量、降低SOD活性,引起肺形态结构的病理变化。氨基胍可明显改善LPS引起的以上肺损伤,病理变化也表明:AG使肺泡萎陷明显减轻,肺间隔变窄,毛细血管增生不明显,肺间隔炎细胞浸润减轻,且高剂量比低剂量明显。结论静脉注射LPS(5 mg/kg)可成功制备大鼠内毒素性肺损伤模型;氨基胍可减轻内毒素性肺损?[ Abstract ] Objective To investigate the effects of inducible NO synthase (NOS) inhibitor aminoguanidine (AG) on endotoxin-induced pulmonary injury in rats. Methods Forty healthy male SD rats weighing 280-320 g were anesthetized with 20% urethane 1-1.2 g kg-1 ip. Right common carotid artery was cannulated for MAP monitoring and left jugular vein was cannulated for medication and blood sampling. The animals were randomly divided into five equal groups : group Ⅰ control; group Ⅱ lipopolysaccharide ( LPS 5 mg kg-1);group Ⅲ high-dose AG (100 mg-kg-1) sgroup IV medium-dose AG (50 mg kg-1) and group V low-dose AG (25 mg kg-1). In group Ⅱ - Ⅴ LPS was given iv 1 h after arterial and venous cannulation was completed. In group I normal saline was given iv instead of LPS. In group DI , IV and V AG was given ip 3 h after LPS. In group Ⅰ and Ⅱ normal saline was given instead of AG. Venous blood samples were taken 1, 3 and 6 h after LPS for determination of plasma NO concentration. The animals were then sacrificed and the lungs were immediately removed for determination of pulmonary coefficient ( lung weight/body weight) , lung water and MDA content, NOS and SOD activities and microscopic examination. Results (1) In LPS group MAP was decreasing after LPS administration. In group III and IV MAP increased significantly after AG administration. (2) In LPS group plasma NO concentration was increasing after LPS and was significantly higher than that in control group at 3 and 6 h after LPS (P <0.05). In group Ⅲ and IV ( high- and medium-dose AG) plasma NO concentration was significantly lower than that in LPS group at 6 h after LPS. (3) In group II NOS activity, MDA and water content in the lungs and pulmonary coefficient were significantly higher than those in control group ( P < 0.01); lung SOD activity was significantly decreased. In group Ⅲ , Ⅳ and Ⅴ pulmonary coefficient, lung MDA content were significantly decreased as compared with those in LPS group (p < 0.01 or0.05) and lung SOD activity was significa

关 键 词：内毒素性肺损伤 氨基胍 一氧化氮 丙二醛 超氧化物歧化酶 

分 类 号：R96[医药卫生—药理学]