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
丁文惠,吴付轩,李大元,朱国英,张钧华,汪丽蕙
摘要(Abstract):
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。
关键词(KeyWords): 心肌梗塞;心肌缺血再灌注损伤;肿瘤坏死因子
基金项目(Foundation): 国家教委基金
作者(Author): 丁文惠,吴付轩,李大元,朱国英,张钧华,汪丽蕙
参考文献(References):
- 1 Squadrito F,Altavilla D,Zingareth B,et al. Tumor necrosisfactor involvement in myocardial ischemia-reperfusion injury.Eur J Phsrmacol,1993,237:223.
- 2 Gurevitch J, Frolkis, Yuhas Y, et al. Tumor necrosis factor-alpha is released from the isolated heart undergoing isChemia and reperfusion JACC,1996,28:247.
- 3 Herskowtz A,Choi S,Ansari AA,et al.Cytokine mRNAexpression in postischemic/reperfusioned myocardium,AmJ Pathol,1995,146:419.
- 4 Suzuki K,Ota H,Sasagawa S,et al.Assay methed for myoperoxidase in human polymorphonuclear leukocytes.Analytical Biochemistry. 1983,132:345.
- 5 Tracey KJ,Vlasara H,Ceremi A.Cachectin/tumor necrosisfactor Lancet,1989,20:1122
- 6 Smitn SC,Alien PM. Neutralization of edogenous tumornecrosis factor ameliorates the seventy of myosin-inducedmyocardtis Circ Res,1992,70:856.
- 7 Maury CPT,Teppo AM.Circulating tumor necrosis factorα(cachectin)in myocardial infarction.J Intern Med,1989,225:333.
- 8 Levine B, Kalman J, Mayer L, et al.Elevated circulatinglevels of tumor necrosis factor in severe chronic heart fail.ure.N Engl J Med,1990,223:236.
- 9 Aoky N,Siegfried M,Lefer AM. Anti-EDRF effect oftumor necrosls factor in isolated Perfused cat carotid arteries.Am J Physiol,1989,256:H1509.
- 10 Mantovani A,E Dejane.Cytokines as communication signals between leukocytes and endothelial cells. ImmunolTodsy,1989,10:370.
- 11 Mullane KM,Kraemer R,Smith R.Myebperoxide activityas an assessment infiltration into ischemic myocardium.JPharmacol Methods,1985,14:157.