大鼠ANP肺损伤中核因子-κB活化对一氧化氮的影响

the potential role of NF-κB activation on the nitric oxide in lung injury of acute necrotizing pancreatitis rats

目的 研究核因子 -κB(NF-κB)活化对大鼠急性坏死性胰腺炎 (ANP)肺损伤中一氧化氮 (NO)的作用。 方法 逆行性胰胆管注射5 %牛磺胆酸钠ANP模型 ,随机分成3组(每组10只) ,对照组 ,ANP组 ,NF-κB抑制剂二硫代氨基甲酸吡咯烷 (PDTC)组。观察模型建立后12h,血清淀粉酶、动脉血氧分压(PaO2)、NO的变化 ,胰腺、肺组织病理变化 ;诱导型一氧化氮合酶(iNOS)及NF-κBp65mRNA在肺组织的表达。结果 PDTC组与ANP组比较 ,血清淀粉酶明显下降 ,由 (8231.20±848.70)U/L降至 (4205.20±1611.49)U/L;NO明显下降 ,由 (178.24±12.00)umol/L降至 (71.00±7.03)umol/L ;胰腺、肺组织损伤减轻 ,iNOS及NF -κBp65mRNA表达下降。结论 抑制NF -κB活化可降低ANP大鼠NO的产生 。

Objective To investigate the potential role of nuclear factor-kappaB(NF-κB) activation on the nitric oxide(NO) in lung injury of acute necrotizing pancreatitis(ANP) rats. Methods Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopanceratic duct. Rats were randomly separated into Control group, ANP group and pyrrolidine dithiocarbamate (PDTC ) group, an inhibitor of NF-κB. At 12 hours of the model, the changes of serum amylase, partial pressure of arterial oxygen (PaO2), NO, pancreas and lung morphological damage were observed. The expressions of inducible nitric oxide synthase (iNOS) were observed by SP immunohistochemistry. NF-κB p65 subunit mRNA expressions were observed by in situ hybridization.Results Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administration group [(8231.20±848.70)U/L vs(4205.20±1611.49)U/L, p <0.05], [(178.24±12.00)umol/L vs(71.00±7.03)umol/L, p<0.05] separately. Though it was still higher than Control group. Pancreas and lung destruction level were lower in PDTC group, iNOS expressions and NF-κB p65 subunit mRNA expressions were lower in PDTC group as compared with ANP group.Conclusions Correlation among NF-κB activation, serum amylase, NO and tissue damage suggests a key role for NF-κB in the pathogensis in lung injury of ANP. Inhibition of NF-κB activation may reverse the lung damage of ANP rats and the production of NO.