摘要
目的观察非选择性一氧化氮合酶(nitric oxide sfynthase,NOS)抑制剂NG-硝基-L-精氨酸(NG-Nitro-L-Arginine,L-NA)和一氧化氮供体L-精氨酸(L-Arginine,L-Arg)对急性肺损伤大鼠肺脏线粒体功能的影响,并探讨其改善急性肺损伤的作用机制。方法将雄性SD大鼠40只随机分为空白对照组、急性肺损伤组、L-NA治疗组和L-NA+L-Arg治疗组、每组8只。L-Arg治疗组,采用舌静脉注射内毒素脂多糖(LPS)复制大鼠急性肺损伤模型,于大鼠急性肺损伤3h后给药治疗3h,断头放血处死,迅速取出大鼠肺脏,匀浆器混匀后,低温差速离心法提取肺脏组织线粒体,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。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(P<0.01),而cNOS活性无明显变化(P<0.05);线粒体总ATP酶、SOD、GSH-Px活性均明显下降(P<0.05或<0.01),线粒体MDA含量明显升高线粒体NO生成明显增加。急性肺损伤3h给予不同药治疗3h与急性肺损伤组比较,肺脏线粒体肿胀降低、膜流动性增强,总ATP酶、SOD、GSH-Px活性均显著升高,MDA含量下降,一氧化氮合酶活性有所显著改变,NO生成量有所不同(P<0.05或<0.01)。结论 L-NA和L-Arg能够通过抑制肺线粒体中iNOS活性,增强eNOS活性,改变NO的产生,对抗内毒素脂多糖导致的氧化损伤,有效的保护肺组织。
Objective To observe the effect of NG-Nitro-L-Arginine （L-NA）and L-Arginine（L-Arg）on mitochondria injury caused by acute lung injury induced by LPS in rats.Methods The rats were randomly devided into blank control group,LPS injury group,L-NA group,L-NA＋L-Arg group and L-Arg group.The models of acute lung injury were prepared with injection of LPS in rat.L-NA and L-Arg were respectively administrated through intraperitioneal injection at 3h after injury induced by LPS,and the rats were killed and the mitochondria of lungs was isolated by differential centrifugation.The activities of T-NOS,iNOS,ATPase,SOD and GSH-Px and the contents of NO and MDA from mitochondria were respectively detected.Results The activities of T-NOS and iNOS were significantly increased,however,the activities of ATPase,SOD and GSH-Px were significantly decreased,and the contents of NO and MDA were increased after acute lung injury.The L-NA and L-Arg could significantly increase ATPase,SOD and GSH-Px activities,and could decrease NO and MDA contents and iNOS activity in mitochondria injury from acute lung injury induced by LPS in rats.Conclusion The L-NA and L-Arg can effectively inhbit the activity of iNOS,enhance the activity of eNOS,improve mitochondria energy pump,change the production of NO,ameliorate oxidative injury,and effectively protect lung tissue against acute lung injury induced by LPS.
出处
《河北医药》
CAS
2010年第17期2309-2312,共4页
Hebei Medical Journal
基金
中国人事部留学人员重点资助项目(编号:9900789)
河北省博士基金资助项目(编号:99547015D)
