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一氧化氮在急性坏死性胰腺炎大鼠肺损伤中的作用 被引量:12

The role of nitric oxide in lung injury associated with acute necrotizing pancreatitis
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摘要 目的 探讨一氧化氮 (NO)在急性坏死性胰腺炎 (ANP)肺损伤中的作用。 方法12 0只成年SD大鼠随机分为正常对照组、ANP组、精氨酸 (L Arg)组、N 硝基 L 精氨酸甲酯 (L NAME)组、混合预处理组 ,每组 2 4只。逆行性胰胆管注射 3%牛磺酸钠建立ANP大鼠模型。经支气管肺泡灌洗获取肺泡巨噬细胞 (AM) ,检测支气管肺泡灌洗液 (BALF)中蛋白含量、肺组织髓过氧化物酶 (MPO)水平、AM分泌肿瘤坏死因子α(TNFα) ,NO水平及TNFαmRNA、诱导型一氧化氮合酶(iNOS)mRNA表达情况。 结果 ANP大鼠肺损伤随着病情进展而逐渐加重 ;肺组织MPO及BALF蛋白含量逐渐升高 ,12h达最高值 ,分别为 (10 8± 0 6 )U/g和 (2 0 11 0± 10 5 5 ) μg/ml;AM分泌TNFα ,NO水平逐渐升高 ,至 6h达到高峰 ,分别为 (16 2 4 2± 14 9 2 ) pg/ml和 (88 8± 6 5 )μmol/L ,12h又回落。AMTNFαmRNA、iNOSmRNA的表达情况与TNFα,NO的变化趋势相似。L Arg、L NAME、混合预处理三组各指标变化趋势与ANP组相似 ,各组与正常对照组相比 ,均有显著性差异 (P <0 0 5 )。L Arg、L NAME组与ANP组相比 ,L Arg组各指标均升高 ,L NAME组各指标均降低 ,差异亦有显著性 (P <0 0 5 )。 结论 由iNOS介导产生的NO的过量生成促进了ANP所致的肺损伤。 Objective To discuss the role of nitric oxide(NO) in lung injury associated with acute necrotizing pancreatitis(ANP). Methods One hundred and twenty SD rats were randomized into five groups:control group, ANP group, L-arginine(L-arg) pretreatment group, L-NAME pretreatment group, and mixed pretreatment group( n =24 for each group). Rat ANP model was induced by intraductal administration of 3% sodium taurocholate. Alveolar macrophages(AMs) were obtained by bronchoalveolar lavage. The protein content of bronchoalveolar lavage fluids(BALF), the myeloperoxidase(MPO) of lung tissue and generation of tumor necrosis factor α(TNFα)and NO by alveolar macrophages were evaluated. The expression of TNFα mRNA and iNOS mRNA was also measured. Results Lung injury was aggravated gradually with progression of the disease. The level of MPO of lung tissue and the protein content of BALF showed a steady increase with time and peaked at the 12 th hour (10.8±0.6 U/g for MPO and 2 011.0±105.5 μg/ml for protein, respectively). TNFα and NO secreted by AMs were elevated gradually and peaked at the 6 th hour (1 624.2±149.2 pg/ml and 88.8±6.5 μmol/L respectively) but decreased at the 12 th hour. The expression of TNFα mRNA and iNOS mRNA was similar with the change of TNFα and NO. The parameters of the groups of L-arg, L-NAME and the mixed pretreatment were similar to those of ANP group. The parameters compared with those of the control group showed a significant difference ( P <0.05). The parameters of groups of L-Arg and L-NAME pretreatment in comparison with those of the ANP group showed significant difference ( P <0.05). Conclusions Over production of NO mediated by iNOS aggravates lung injury caused by acute necrotizing pancreatitis. Administration of exogenous NOS substrate would worsen lung injury, whereas administration NOS inhibitor would alleviate lung injury.
出处 《中华外科杂志》 CAS CSCD 北大核心 2003年第5期336-339,共4页 Chinese Journal of Surgery
关键词 一氧化氮 急性坏死性胰腺炎 大鼠 肺损伤 支气管肺泡灌洗 并发症 Nitric oxide Pancreatitis, acute necrotizing Lung diseases,interstitial Macrophages, alveolar Tumor necrosis factor Nitric oxide synthase
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