N^G-硝基-L-精氨酸对大鼠内毒素性肺线粒体损伤的影响  

Effect of N^G-nitro-L-arginine on mitochondria in acute lung injury induced by LPS in rats

作　　者：尚涛[1] 张建新[1] 李兰芳[1] 李立萍[1] 李国风[1] 解丽君[1] 郝娜[1] 武宏敏[1] 

机构地区：[1]河北省医学科学院药物研究所,河北石家庄050021

出　　处：《中国病理生理杂志》2008年第5期920-924,共5页Chinese Journal of Pathophysiology

基　　金：国家人事部留学人员重点资助项目(No.9900789);河北省博士基金资助项目(No.99547015D)

摘　　要：目的:观察非选择性一氧化氮合酶(NOS)抑制剂NG-硝基-L-精氨酸(L-NA)对急性肺损伤大鼠肺线粒体功能的影响,并探讨其改善急性肺损伤的作用机制。方法:将SD大鼠随机分为空白对照组、急性肺损伤组、L-NA治疗组,采用舌静脉注射脂多糖(LPS)复制大鼠急性肺损伤模型,于大鼠急性肺损伤3h后给L-NA治疗3h,断头放血处死大鼠,迅速取出肺脏,匀浆器混匀后,低温差速离心法提取肺线粒体,测定线粒体总ATP酶、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、总一氧化氮合酶(T-NOS)、诱生型一氧化氮合酶(iNOS)、结构型一氧化氮合酶(cNOS)的活性,以及线粒体肿胀度、膜流动性和线粒体一氧化氮(NO)、丙二醛(MDA)含量;电镜观察大鼠肺线粒体超微结构的改变及治疗药对此改变的影响。结果:在大鼠内毒素性急性肺损伤后,肺脏组织中线粒体表现为肿胀、膜流动性降低,线粒体中的T-NOS和iNOS活性显著升高,线粒体NO生成明显增加,而cNOS活性无明显变化;线粒体总ATP酶、SOD、GSH-Px活性均明显下降,线粒体MDA含量明显升高。急性肺损伤3h给予L-NA治疗3h,与急性肺损伤组相比,一氧化氮合酶活性有所改变,NO生成显著下降,总ATP酶、SOD、GSH-Px活性均显著升高,MDA含量下降。电镜结果显示内毒素性急性肺损伤后肺脏组织细胞水肿,线粒体肿胀、嵴断裂、溶解、消失;L-NA能改善内毒素性急性肺损伤引起的细胞水肿、线粒体肿胀和空泡化。结论:L-NA能明显抑制急性肺损伤后线粒体一氧化氮合酶活性,减少NO生成,改善线粒体能量供应,增加线粒体抗氧化作用,从而减轻急性肺损伤。AIM： To examine the effect of nonselective nitric oxide synthase inhibitor, N^G- nitro - L - argi- nine （L- NA）, on mitochondria from acute lung injury induced by lipopolysaccharides（LPS） in rats. METHODS： The rats were randomly divided into control group, LPS injury group and L - NA treatment group. The model of acute lung injury was prepared with injection of LPS in rats. L - NA was respectively administrated through intraperltoneal injection at 3 h after injury induced by LPS. The rats were killed and the mitochondria in lung tissues were isolated by differential eentrifu- gntion. The activities of T - NOS, iNOS, ATPase, SOD and GSH - Px, and the contents of NO and MDA from mitochon- dria were respectively measured. The changes of uhrastructure in lung mitochondria were examined by electronic microscope after injury and L - NA treatment. RESULTS： The activities of T - NOS and iNOS were significantly increased, the activities of ATPase, SOD and GSH -Px were significandy decreased, the contents of NO and MDA were increased after acute lung injury. L - NA significantly enhanced the activities of ATPase, SOD and GSH - Px, and markedly decreased the contents of NO and MDA and the activities of T - NOS and iNOS. CONCLUSION： L - NA inhibits the activity of NOS in mitochondria, decreases the production of NO, improves mitochondria energy pump, ameliorates oxidative injury, and effec- tively protects lung tissue against acute lung injury induced by LPS.

关 键 词：肺损伤 线粒体 精氨酸 脂多糖类 一氧化氮 

分 类 号：R363[医药卫生—病理学]