目的:探索脓毒症脑组织线粒体功能及可能损伤机制.方法:选取40只清洁级雄性SD大鼠(180～220 g),以抽签方式随机分为4组:正常对照组,3 h脓毒症组(3LPS组),6h脓毒症组(6LPS组)和24 h脓毒症组(24LPS组),每组10只.腹腔注射革兰阴性菌脂多糖(LPS)溶液建立脓毒症大鼠动物模型,各脓毒症组大鼠在相应时点处死后分离获得线粒体.测定各组大鼠脑线粒体膜电位、线粒体丙二醛(mtMDA)含量、线粒体一氧化氮合酶(mtNOS)活性以及线粒体一氧化氮(mtNO)浓度.结果:3LPS组大鼠脑线粒体膜电位较正常对照组明显降低[(0.5±0.5)vs(1.2±0.6),P＜0.05];6LPS组和24LPS组大鼠脑线粒体膜电位与正常对照组无明显差异[(1.4±0.7)vs(1.2±0.6),(1.6±0.7)vs(1.2±0.6)].3LPS组和6LPS组大鼠脑mtMDA含量较正常对照组明显升高[(12.0±2.1)μmol/Lvs(5.7±0.8)μmol/L,(8.7±0.8)μmol/Lvs(5.7±0.8)μmol/L,P＜0.01];24LPS组大鼠脑mtMDA含量较正常对照组无明显差别[(6.5±1.6)μmol/L vs(5.7±0.8)μmol/L].3LPS组和6LPS组大鼠脑mtNOS活性较正常对照组明显升高[(74±24)μkat/g vs(16±13)μkat/g,P＜0.01;(32±10)μkat/g vs(16±13)μkat/g,P＜0.05];24LPS组大鼠脑mtNOS活性较正常对照组无明显差别[(28±12)μkat/g vs(16±13)μkat/g].3LPS组、6LPS组和24LPS组大鼠脑mtNO浓度均较正常对照组明显升高[(15.4±4.8)μmol/g vs (1.2±2.6)μmol/g,(6.5±3.8)μmol/g vs(1.2±2.6)μmol/g,(3.6±2.1)μmol/g vs (1.2±2.6)μmol/g,P＜0.01].脓毒症大鼠脑mtMDA含量、mtNOS活件和mtNO浓度与脑线粒体膜电位存在明显负相关性(r=-0.677,P＜0.01;r=-0.738,P＜0.01;r=-0.715,P＜0.01).结论:大鼠脓毒症病程中存在可逆性脑线粒体功能损伤;脓毒血症时脑线粒体损伤发生高峰在3～6 h;氧化应激是导致脓毒症大鼠脑线粒体功能损伤的主要机制之一,其中mtNOS和mtNO在这一机制中发挥了重要作用.
Preliminary study on cerebral mitochondrial dysfunction in septic rats
AIM:To study the pathogenesis of cerebral mitochon-drial dysfunction in septic rats. METHODS: Forty clean level SD male rats were randomly divided into 4 groups: control group,3-h sepsis group,6-h sepsis group and 24-h sepsis group. The sepsis model was established by intraperitoneal injection of lipopolysaccha-ride( LPS,from Escherichia coli 0111 :B4). Cerebral mitochondrial membrane potential was determined and the levels of MDA,NOS and NO in cerebral mitochondria were also determined. RESULTS: Cerebral mitochondrial membrane potential in 3-h sepsis group decreased significantly compared with that in control group[ (0.5 ±0.5) vs (1.2 ±0.6) ]. The cerebral mitochondrial MDA concentration in 3-h and 6-h sepsis groups increased significantly compared with that in control group[ (12.0 ± 2.1) μmol/L vs (5.7 ±0. 8)μmol/L,(8. 7 ±0. 8)μmol/L vs (5.7 ±0.8) μmol/L]. The cerebral mitochondrial NOS activity in 3-h and 6-h sepsis groups increased significantly compared with that in control group[(74±24)μkat/g vs (16 ±13)μkat/g,(32 ±10)μkat/g vs (16 ± 13) μkat/g]. The cerebral mitochondrial NO concentration in all septic groups increased significantly compared with that in control group[( 15.4±4.8)μmol/gra (1.2±2.6)(± μmol/g,(6.5 ± 3.8) μmol/g vs (1. 2 ±2. 6) μmol/g,(3.6±2.1) μmol/g vs (1.2 ±2. 6) μmol/g]. The cerebral mitochondrial MDA,NOS and NO showed significant negative linear correlations with cerebral mitochondrial membrane potential (r = -0.677,P < 0. 01;r = -0.738,P<0.01;r= -0.715,P<0.01). CONCLUSION: There is reversible cerebral mitochondrial dysfunction in septic rats. Oxidative stress is a main pathogenic cause of cerebral mito- chondrial dysfunction in septic rats. mtNOS and mtNO play some important roles in cerebral mitochondria oxidative stress injury.
NETL
NSTL
万方数据
维普
