抑制低氧诱导因子-1α表达对小鼠肠缺血／再灌注所致肺损伤的影响  

The effects of inhibiting the expression of hypoxia inducible factor-lot on lung injury induced by intestinal ischemial repeffusion in mice

作　　者：徐睿[1] 李启芳[1] 姜虹[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院麻醉科,200011

出　　处：《国际麻醉学与复苏杂志》2013年第11期986-989,共4页International Journal of Anesthesiology and Resuscitation

基　　金：上海市自然科学基金（12ZR1417200）

摘　　要：目的探讨通过低氧诱导因子-1α（hypoxiainduciblefactor-1α，HIF—1α）抑制剂YC-1预先抑制该基因表达对肠缺血，再灌注（ischemia／reperfusion，I／R）致急性肺损伤的影响。方法6周～8周龄健康雄性C57BL／6小鼠36只，采用随机数字表法随机分为3组（每组12只）：假手术组（S组）、I／R组和I／R±YC—I预处理组（YC—I组）。YC-1组于术前10min腹腔注入YC-1（1mg／kg），采用夹闭C57BL／6小鼠肠系膜前动脉45min后再灌注6h的方法造成肠YR损伤模型，取小鼠肺标本称重后计算肺湿干重比，苏木素-伊红（hematoxylin-eosin，HE）染色后观察肺组织病理学改变，分光光度法测定髓过氧化物酶（myeloperoxidase，MPO）活性、酶联免疫吸附测定法检测肺组织肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素（interleukin，IL）-1β表达，反转录-PCR法检测HIF-1α、Toll样受体4（toll—likereceptor4，TLR4）mRNA的表达。结果与I／R组比较，预先抑制HIFqct表达使肺实质水肿及中性粒细胞浸润聚集减少，肺组织病理学损伤减轻，肺湿干重比显著降低（RnOI），MPO活性下调[（1．88±0．82）u／g]，TNF-α[（187±20）ng／L）]、IL一1β[（536±54）ng／L）]、HIF-1α、TLR4mRNA的表达水平下降（P〈0．05）。结论YC-1预处理可使肺组织TLR4mRNA表达下调，抑制肠I／R肺组织中促炎细胞因子的释放，明显减轻小鼠肠I／R后急性肺损伤。Objective To investigate the effect of pretreatment with hypoxia inducible factor-1α（HIF-1α） inhibitor （YC-1） on Toll-like receptor 4（TLR4 ） mRNA expression in the lung following acute lung injury induced by intestinal ischemia/reperfusion（ I/R ） injury in mice. Methods Thirty-six healthy male C57BL/6 mice weighing 20 g-24 g were randomly divided into 3 groups （n=12）： sham operation group（group S） ;intestinal I/R group （group I/R） and YC-1 administration before ischemia group （group YC-1）. 1 rag/ kg YC-1 was injected intraperitoneally at 10 rain before ischemia in group YC-1. Intestinal I/R injury was induced by clamping the superior mesenteric artery for 45 min and the mice were sacrificed at 6 h of reperfusion. The lungs were immediately removed for subsequent microscopic examination, determination of W/D lung weight radio and myeloperoxidase （MPO） activity, levels of tumor necrosis factor-et（TNF-α） and intedeukin（IL）-1β, HIF-1α and TLR4 mRNA expression in the lung tissue（by reverse transcription- PCR）. Results Microscopic examination showed that there existed collapse or consolidation of alveoli, edema and infiltration of neutrophils in the lung parenchyma in I/R group. Intestinal I/R injury significantly increased W/D lung weight ratio, MPO activity, levels of TNF-α and IL-1β, HIF-1α and TLR4 mRNA in the lung tissue. The lung injury was significantly ameliorated in group YC-1 as compared with group I/R. Pretreatment with YC-1 significantly inhibited intestinal isehemia reperfusion-induced increase in W/D lung weight ratio（4.35±0.20）, MPO activity[ （1.88±0.82） U/g], levels of TNF-α[ （187±20） ng/L） ] and IL-1β [ （536±54） ng/L） ], HIF-1β and TLR4 mRNA in the lung tissue. Conclusions YC-1 pretreatment before ischemia can reduce acute lung injury induced by intestinal I/R through down-regulation of TLR4 mRNA expression and decreasing levels of TNF-α and IL-1β in the lung.

关 键 词：YC-1 低氧诱导因子-1Α 缺血 再灌注 肠 肺 TOLL样受体4 

分 类 号：R363[医药卫生—病理学]