内毒素耐受大鼠肺部iNOS和NO表达的动态变化和意义  

Pulmonary iNOS and NO production during LPS-initiated lung inflammation in endotoxin tolerance rats

作　　者：汤睿[1] 孙瑞玥[1] 周亚光[1] 苏明华[1] 杨光田[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院急诊科,武汉430030

出　　处：《中国急救医学》2008年第1期42-45,共4页Chinese Journal of Critical Care Medicine

基　　金：湖北省科技攻关计划项目资助(No.2003AA301C51)

摘　　要：目的研究内毒素血症时内毒素耐受大鼠肺部诱导型一氧化氮合酶(iNOS)、一氧化氮(NO)的动态变化。方法72只SD大鼠随机分为对照组(NC组)和内毒素耐受组(ET组)。腹腔注射小剂量内毒素(LPS),第1天0.1mg/只;第2～5天0.5mg/只,建立内毒素耐受模型。NC组腹腔注射同等剂量生理盐水。最后一次注射LPS72h后,两组均腹腔注射大剂量LPS(10mg/kg)。各组按注射LPS前(0h),注射后2、4、6、12、24h分为六小组(n=6)。通过比色法(即Griess法)测量肺组织iNOS、NO、丙二醛(MDA)及髓过氧化物酶(MPO)含量。同时在第6、12h取大鼠左下肺组织行组织病理形态学观察。用SPSS13.0统计软件进行统计分析。结果NC组大鼠在大剂量LPS刺激后肺组织iNOS和NO在4h开始升高,6～12h达到高峰(P<0.05);MDA和MPO含量在2h即开始升高,4～12h达到高峰(P<0.05)。ET组大鼠在大剂量LPS刺激前肺组织iNOS、NO、MDA和MPO即有微量升高(P>0.05),大剂量LPS刺激后肺组织iNOS、NO、MDA和MPO亦有升高,但与NC组相比明显降低(P<0.05)。病理学检查显示,ET组肺组织损伤明显较NC组减轻。结论内毒素耐受时,大剂量内毒素血症引起的大鼠肺部损伤减轻与肺部iNOS、NO低表达有关。Objective To study the pulmonary inducible nitric oxide synthase（iNOS）and nitric oxide（NO）production of endotoxin tolerance rats in endotoxemia.Methods Seventy-two Sprague-Dawley male rats were randomized into endotoxin tolerance（ET）group and normal control（NC）group.Endotoxin tolerance was induced by intraperitoneal injection of 0.25 mg/rat Escherichia coli LPS（serotype 0127：B8）at the first day and intraperitoneal injection of 0.5mg/rat LPS on days 25.NC group received intraperitoneal injections of the same volume saline.72 hours after the last LPS injection,all rats were intraperitoneally injected with high dose of LPS（10 mg/kg）to induce endotoxemia and lung inflammation.Right lung tissue were collected before and 2,4,6,12,24 hours after the high dose injection of LPS（six rats for each time point）.The production of pulmonary iNOS,NO,MPO and MDA were measured by Griess.The histological change of the left lung at the 6 and 12 hour were observed under light microscope.Software SPSS13.0 was utilized for statistical analysis.Results Before high dose LPS challenge,all the four variables in ET group were slightly elevated,but did not reach statistical meaning compared with NC group.In NC group,the level of four variables were respectively significantly increased from 4 h to 12 h after challenge.As contrasted,the four variables were increased a little in ET group.Under the light microscope,the pathologic change induced by high dose of LPS were significantly attenuated in the ET group.Conclusions The induction of rat endotoxin tolerance is associated with a profoundly low level of iNOS,NO,MPO and MDA production in lung tissue when they are challenged with high dose LPS.

关 键 词：内毒素耐受 一氧化氮 诱导型一氧化氮合酶 肺损伤 

分 类 号：R563.8[医药卫生—呼吸系统]