TNF-α、ICAM-1在心肌无复流中的表达与调节机制

Expressions of TNF-α and ICAM-1 during myocardial ischemia/reperfusion and related regulatory mechanism

目的:研究肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、细胞间黏附分子-1(intracellular adhesion molecules-1,ICAM-1)在家兔心肌无复流模型血浆中的表达水平及调节机制。方法:30只新西兰大白兔,随机分为假手术组、心肌缺血再灌注组和四氢吡咯二硫代氨基甲酯(pyrrolidine dithiocarbamate,PDTC)组(缺血前30 min经耳缘静脉注射PDTC 20 mg/kg)。心肌缺血再灌注组和PDTC组采用开胸冠状动脉结扎回旋支90 min再松解60 min的方法建立家兔心肌无复流模型。通过酶联免疫吸附试验测定各组家兔缺血再灌注过程中炎症因子TNF-α和ICAM-1在血浆的表达水平、测定心肌不同区域心肌髓过氧化酶(myeloperoxidase,MPO)活性、光镜及电镜下观察心肌细胞受损情况。结果:家兔心肌缺血再灌注组炎症因子TNF-α和ICAM-1的表达水平在缺血后150 min时达高峰,明显高于PDTC组(P<0.05)。心肌缺血再灌注组无复流区及缺血区心肌MPO活性较假手术组和PDTC组均明显升高(P<0.05)。PDTC组无复流区心肌细胞损伤程度轻于缺血再灌注组。结论:家兔心肌缺血再灌注诱导炎症因子的表达;抑制核因子-κB激活可减少无复流区的中性粒细胞浸润和激活,减少炎症因子的表达,减轻无复流区心肌再灌注损伤程度。

Objective：To investigate the release of pro-inflammatory mediators：tumor necrosis factor-α（TNF-α）and intracellular adhesion molecules-1（ICAM-1）during myocardial ischemia/reperfusion and related regulatory mechanism. Methods：Totally 30 New Zealand white rabbits were divided into 3 groups：sham group, cardiac ischemia/reperfusion group（the left circumflex coronary arteries of the rabbits were ligated for 90 min then untied for 60 min）and PDTC group（20 mg/kg pyrrolidine dithiocarbamate was injected intravenously 30 min before cardiac ischemia）.Plasma levels of ICAM-1 and TNF-α at different time points during ischemia/reperfusion were detected by ELISA. Myocardial myeloperoxidase activities in different regions were determined and myocardial cell injury was observed under the light microscope and electron microscope. Results：Serum concentration of TNF-α and ICAM-1 in cardiac ischemia/reperfusion group reached the peak 150 min after myocardial ischemia,which was significantly higher than that of sham group and PDTC group（P＆lt;0.05）. Myeloperoxidase in no-reflow area and ischemic area was significantly higher in ischemia/reperfusion group than in sham group and PDTC group（P＆lt;0.05）. Histological results showed that myocardial injury in no-reflow area was less severe in PDTC group than in ischemic/reperfusion group. Conclusions：Cardiac ischemic/reperfusion can promote the release of pro-inflammatory mediators. Inhibition of nuclear factor-κB can decrease the infiltration and activation of neutrophile granulocyte,attenuate the release of pro-inflammatory factors and decrease myocardial injury in no-reflow area.