内源性一氧化氮/一氧化氮合酶体系及一氧化碳/血红素合酶体系对大鼠肝硬化门静脉压力的影响  

Effect of endogenous nitric oxide/nitric oxide synthase and carbon monoxide/heme oxygenase-1 on portal pressure in rats with hepatic cirrhosis

作　　者：宋丽秀[1] 陈卫刚[1] 郑勇[1] 张宁[1] 齐翠花[1] 

机构地区：[1]石河子大学医学院第一附属医院消化内科,新疆维吾尔自治区石河子市832000

出　　处：《世界华人消化杂志》2014年第19期2686-2691,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30850004~~

摘　　要：目的:研究内源性一氧化氮(nitric oxide,NO)/一氧化氮合酶(nitricoxide synthase,NOS)体系及一氧化碳(carbonic oxide,CO)/血红素合酶(heme oxygenase,HO-1)体系对肝硬化大鼠门静脉压力的影响,探讨NO/NOS体系及CO/HO-1体系在大鼠肝硬化门静脉高压中的作用.方法:将SD大鼠随机分为4组:正常对照组(N C组)、正常对照+左旋硝基精氨酸甲酯(L-NAME)+锌原卟啉-Ⅸ(Znpp-Ⅸ)组(NC+LNAME+ZnPP-Ⅸ组)、肝硬化模型组(CIRM组)、肝硬化模型+左旋硝基精氨酸甲酯(L-NAME)+锌原卟啉-Ⅸ(Znpp-Ⅸ)组(CIRM+LNAME+ZnPP-Ⅸ组).均用插管法测定门静脉压力,用硝酸还原酶法测定血浆中NO含量,联二亚硫酸盐还原法测定血浆CO含量,运用蛋白免疫印迹技术(Western blot)测定肝组织中内皮细胞一氧化氮合酶(endothelial nitricoxide synthase,e N O S)、诱导型一氧化氮合酶(i n duc i b l e nitricoxide synthase,iNOS)及HO-1蛋白的表达情况.结果:与NC组相比,CIRM组血浆NO、CO含量明显升高(160.12μmol/L±4.18μmol/L,111.12μmol/L±2.26μmol/L vs 81.11μmol/L±2.91μmol/L,70.51μmol/L±3.10μmol/L,均P<0.01),门静脉压力明显升高(16.08 mmHg±1.16 mmHg vs 9.85 mmHg±1.10 mmHg,P<0.01),肝组织中iNOS及HO-1蛋白含量明显升高(165.69±1.17,155.79±1.29 vs 135.22±0.54,125.44±0.94,均P<0.01),但eNOS在肝组织的表达却明显降低(118.65±1.29 vs 160.77±2.12,P<0.01),而NC+L-NAME+ZnPP-Ⅸ组NO、CO含量则明显降低(52.06μmol/L±3.17μmol/L,52.51μmol/L±2.63μmol/L,均P<0.01),门静脉压力无统计学意义,肝组织中eNOS、iNOS及HO-1蛋白含量亦明显降低(130.83±1.57,120.81±1.47,111.03±1.45,均P<0.01);与CIRM组相比,CIRM+L-NAME+ZnPP-Ⅸ组血浆NO、CO含量明显降低(100.24μmol/L±3.80μmol/L,83.73μmol/L±1.78μmol/L,均P<0.01),门静脉压力明显降低(14.13 mmHg±0.56 mmHg,P<0.01),肝组织中eNOS、iNOS及HO-1蛋白含量明显降低(87.50±1.07,150.66±1.42,139.88±1.73,均P<0.01).结论:NO、CO作为新型气体信号分子,与肝硬化门静脉AIM： To assess the effect of endogenous nitric oxide/nitric oxide synthase（NO/NOS） and car-bon monoxide/heme oxygenase-1（CO/HO-1） on the portal pressure（PP） in rats with hepatic cirrhosis, and to explore the role of NO/NOS and CO/HO-1 system in the development of portal hypertension（PH）. METHODS： Sprague-Dawley rats were ran-domly divided into three groups： a normal control group（NC）, a cirrhosis model group（CIRM）, and a cirrhosis model ＋ L-NAME ＋ ZnPP-Ⅸ group（CIRM ＋ L-NAME ＋ ZnPP-Ⅸ）. PP was measured using indwelling catheters. Plasma concentration of NO was detected using the nitrate reductase method, and the plasma CO was measured using the Chalmers method. The expression and localization of Enos, iNOS and HO-1 in endothelial cells of the portal vein（PV） were studied by immunohistochemistry. Western blot was used to analyze hepatic tissue eNOS, iNOS and HO-1 protein expression. RESULTS： Compared with the NC group, the CIRM group had significant increases in plasma NO and CO（160.12 μmol/L ± 4.18 μmol/L, 111.12 μmol/L ± 2.26 μmol/L vs 81.11 μmol/L ± 2.91 μmol/L, 70.51 μmol/L ± 3.10 μmol/L, P〈0.01）, PP（16.08 mmHg ± 1.16 mmHg vs 9.85 mmHg ± 1.10 mmHg, P〈0.01）, and the expres-sion of eNOS, iNOS and HO-1（165.59 ± 1.71, 164.66 ± 1.34, 166.38 ± 1.17, P〈0.01）, but a sig-nificant decrease in hepatic expression of eNOS（118.65 ± 1.29 vs 160.77 ± 2.12, P〈0.01）; howev-er, the NC ＋ L-NAME ＋ ZnPP-Ⅸ group showed significant decreases in plasma NO and CO（52.06 μmol/L ± 3.17 μmol/L vs 52.51 μmol/L ± 2.63 μmol/L, P〈0.01）, and the hepatic expression of eNOS, iNOS and HO-1（130.83 ± 1.57, 120.81 ± 1.47, 111.03 ± 1.45, P〈0.01）, although the PP showed no significant difference. Compared with the CIRM group, the CIRM ＋ L-NAME ＋ ZnPP-Ⅸ group had significant decreases in plas-ma NO and CO（100.24 μmol/L ± 3.80 μmol/L, 83.73 μmol/L ± 1.78 μmol/L, P〈0.01）, PP（14.13 mmHg ± 0.56 mmHg, P〈0.01）, and h

关 键 词：一氧化氮 一氧化碳 一氧化氮合酶 血红素氧合酶 肝硬化 门静脉高压 

分 类 号：R575.2[医药卫生—消化系统]