内源性CO和NO在大鼠脑缺血-再灌注损伤中的作用  

Interactions between endogenous carbon monoxide and nitric oxide during rat global cerebral ischemic-reperfusion injury

作　　者：周银燕[1] 邵建林[1] 赵国良[1] 梁荣毕[1] 钟颖[1] 

机构地区：[1]昆明医学院第一附属医院手术麻醉科,650032

出　　处：《临床麻醉学杂志》2011年第4期404-407,共4页Journal of Clinical Anesthesiology

基　　金：云南省科技厅面上项目(2008CD120);云南省教育厅科学研究基金(08C0110);昆明医学院第一附属医院博士科研启动基金(2007bs10)

摘　　要：目的研究血红素氧合酶-1(heme oxygenase-1,HO-1)/一氧化碳(CO)体系和诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)/一氧化氮(NO)体系在大鼠脑缺血-再灌注损伤中的相互作用,探讨脑保护策略。方法 24只Wistar大鼠随机均分为四组:脑缺血-再灌注+锌原卟啉组(Z组)、脑缺血-再灌注+氨基胍组(A组)、脑缺血-再灌注组(IR组)、假手术组(C组)。Z组和A组夹闭两侧颈总动脉前30 min腹腔分别注射锌原卟啉45μmol/kg或氨基胍500 mg/kg,C组和IR组腹腔注射等量生理盐水。缺血20 min再灌注6 h后处死大鼠取海马,检测大鼠海马组织中CO、NO、SOD、MDA量的变化及HO-1-mRNA和iNOS-mRNA表达水平;电镜观察海马线粒体的变化。结果与C组相比,IR组CO、NO、MDA的含量增高,SOD降低,HO-1-mRNA和iNOS-mR-NA表达增高(P<0.01),电镜观察线粒体受损。与IR组相比,Z组CO和SOD的量降低,NO、MDA的量增高,HO-1-mRNA的表达降低(P<0.01),电镜观察线粒体受损加重;A组NO、MDA的量降低,SOD的量增高,iNOS-mRNA表达降低(P<0.01),电镜观察线粒体受损减轻。结论脑缺血-再灌注损伤过程中,iNOS/NO体系介导了神经细胞的损伤,而HO-1/CO体系具有抗损伤的作用;iN-OS抑制剂在脑缺血-再灌注损伤过程中对神经细胞有保护作用。Objective To investigate the interaction between HO-1/CO and iNOS/NO systems during global cerebral ischemia-reperfusion （IR） injury and retrieval brain protection methods. Methods Twenty four Wistar male rates aged 3-4 months were equally randomized into 4 groups： control （C） group, IR group, IR ＋ aminoguani dine （A） group, IR ＋ zinc-protoporphyrin （Z） group. Global cerebral LR was established by 4-vessel occlusion. Group C was carried out sham operation. Group A and Group Z rats were respectively intraperitoneal injected 500 mg/kg aminoguanidine or 45 μmol/kg zinc protoporphyrin before 30 min of clasping bilateral carotid artery, group C and group IR were injected equation saline The carotid clasps were removed after 20 min of 4-vessle occlusion and rates were killed after 6 h of repeffusion. The concentration of CO, NO, MDA, the activity of SOD, arid expression of HO-1 mRNA and iNOS mRNA in rats＇ hippocampus were measured. The mitochondrial structure was observed by electronmicroscope. Results The concentration of NO, CO and MDA was significantly increased, SOD was significantly decreased,iNOS-mRNA and HO-I-mRNA expression has increased in group IR as compared with group C （P〈0. 01）. Meanwbile the structure of mitochondrial has destroyed. Group A level of NO and MDA were decreased, but SOD were increased, iNOS-mRNA expression was decreased compared with group IR（P〈 0. 01 ）, mitochondrial destroying has mitigated. Group Z CO and SOD were significantly decreased, but level of NO and MDA were increased, HO-1-mRNA was decreased as compared with group IR（P〈0. 01）, mitochondrial destroying has aggravated. Conclusion iNOS/NO system can induce nerve cells damage, but HO1/CO plays an against-damage role in cerebral ischemia-reperfusion. Inhibitor of iNOS has possessed neuroprotective effects.

关 键 词：一氧化碳 一氧化氮 缺血再灌注损伤 血红素氧合酶-1 诱导型一氧化氮合酶 

分 类 号：R743[医药卫生—神经病学与精神病学]