肿瘤坏死因子在心肌缺血再灌注中的变化和意义

The Changes and Significance of Serum Tumor Necrosis Factor-α in Myocardial Ischemia-reperfusion

为探讨肿瘤坏死因子-α（TNF－α）在心肌缺血再灌注治疗中的变化及其意义，观察了急性心肌梗塞（AMI）溶栓治疗后血管再通与未通患者血浆TNF－α含量的动态变化，同时在兔心肌缺血再灌注（MI／R）模型上观察了血浆TNF－α、心肌组织中中性粒细胞的浸润、髓过氧化物酶（MPO）活性和丙二醛（MDA）含量。结果显示：（1）AMI发病早期（6h）血浆TNF－α含量高于正常对照31％（P＞0．05）；溶栓血管未通患者在发病24小时内较正常升高33．2％～38．6％（P＞0．05）；溶栓血管开通后在再灌注1小时较正常对照和溶栓前分别升高达76．7％和44．6％（P＜0．01，P＜0．05），再灌注4．5小时仍高于正常对照（P＜0．05），10小时后下降接近溶栓前水平。动物实验与临床结果相似，并发现，缺血与坏死心肌中有大量中性粒细胞浸润；MI1．5h／R1h或R4h组较MI1．5h组缺血心肌中MPO活性与MDA含量均明显升高（P＜0．05，P＜0．01），TNF－α释放与MPO活性呈正相关（γ＝0．72，P＜0．01）。结果提示，TNF－α参与了心肌缺血再灌注损伤的发病，TNF－α可能促进了中性粒细胞对心肌的浸润并与中性粒细胞共同导致了心肌损伤。

In order to investigate the change and significance of tumor necrosis factor-α (TNF-α) in myocardial ischemia-reperfusion,the changes of serum TNF-Q concentration were observed in patients suffering from acute myocardial infarction (AMI) with reperfusion and without reperfusion after intravenous thrombolytic therapy. In a rabbit model with myocardial ischemia-reperfusion (MI/R), the changes of serum TNF-α,the infiltration of polymorphonuclear leukocytes (PMNs),myoperoxidase (MPO) and malodialdehyde (MDA) content in the myocardium were determined. The results were as follows: (1) serum TNF-α level at early phase of onset (6 hours) was 31% higher than those of the controls (P>0.05). In the patients without reperfusion, the serum TNF-α levels were 33.2 %~38. 6 % higher than those of the controls within 24 hours of onset (P>0.05). However, serum TNF-a levels at 1 hour after reperfusion were 76%, 44. 6% higher than those of the controls and before reperfusion respectively (P<0.01, P<0.05),at 4.5 hours it was still significantly higher than that of controls,at 10 hours serum TNF-α gradually decreased to the level before reperfusion in the patients with reperfusion. (2) In rabbit model with MI/R and MI,the changes of serum TNF-α were similar to those AMI patients. In addition,lots of PMNs infiltraied in the ischemic and necrotic areas of myocardium. Myocardial MPO activity and MDA content of ischemic area of MI1. 5 h/R1 h or MI 1. 5 h/R4 h group significantly increased than that of MI1. 5 h group (P<0. 05,P<0.01).TNF-2 release correlated with MPO activity (γ=0. 72,P<0.01). The results suggest that TNF-α participate in pathogenesis of myocardial ischemia-reperfusion injury,it might accelerate PMNs infiltrating myocardium and both of them result in myocardial damage.