白介素-1受体拮抗剂对缺血再灌注心肌的保护作用及其机制探讨  

The protective effect of interleukin-1 receptor antagonist on postischemic reperfused myocardium and its possible mechanism

作　　者：李拥军[1] 丁文惠[1] 高炜[1] 霍勇[1] 洪涛[1] 朱仁英[2] 马大龙[3] 

机构地区：[1]北京大学第一医院心内科,100034 [2]北京北医联合生物工程有限公司 [3]北京大学人类疾病基因中心

出　　处：《中华医学杂志》2004年第7期548-553,共6页National Medical Journal of China

基　　金：教育部教育振兴行动计划特殊专项基金资助项目 (8810 5 612 2 0 10 13 ) ;首都医学发展科研基金资助项目 (2 0 0 2~ 2 0 0 3 )

摘　　要：目的　探讨急性心肌梗死 (AMI)再灌注过程中白介素 - 1β(IL 1β)的变化及重组人白介素 - 1受体拮抗剂 (rhIL 1ra)对缺血再灌注心肌的保护作用及其机制。方法　 (1)用ELISA法测定了 8名健康人和 2 2例接受急诊经皮冠脉介入治疗 (PCI)并且梗死相关血管 (IRA)血流达心肌梗死溶栓 (TIMI) 3级的AMI患者血浆IL 1β水平的动态变化。 (2 )在兔心肌缺血 5 0min再灌注 4h的模型上 ,观察不同剂量rhIL 1ra(A组 :rhIL 1ra 10mg/kg ;B组 :rhIL 1ra 2 0mg/kg ;C组 :rhIL 1ra 4 0mg/kg)对心肌梗死面积、心肌髓过氧化物酶 (MPO)活性、心肌细胞凋亡程度 (TUNEL、AnnexinⅤ和DNA 梯形图法 )及凋亡相关基因Bcl 2 /Bax的表达。结果　 (1) 2 2例AMI患者再灌注前血浆IL 1β(2 8pg/ml±9pg/ml)已明显高于健康对照组 (2 0 pg/ml± 11pg/ml,P <0 0 5 ) ,IRA再通后 12h血浆IL 1β水平达高峰 (86 pg/ml± 14pg/ml) ,至术后 2 4hIL 1β血浆水平 (5 6 pg/ml± 15 pg/ml)仍明显高于再灌注前 (2 8pg/ml± 9pg/ml,P <0 0 1)。 (2 )兔AMI对照组与rhIL 1ra各组之间心肌缺血面积差异均无显著意义 ,但各rhIL 1ra组梗死心肌面积均小于对照组 ,组间差异呈剂量依赖性 (47%±7% ,34%± 8% ,31%± 6 %比 6 1%± 11% ,分别PObjective To observe the dynamic changes of plasma inflammatory cytokine interleukin-1β (IL-1β) in patients with acute myocardiac infarction (AMI) before and after recanalization of the infarct related artery (IRA) and to observe the effect of recombinant human IL-1 receptor antagonist (rhIL-1ra) on the postischemic reperfused myocardium in experimental rabbits.Methods (1) ELISA was used to measure the plasma IL-1β of 22 AMI patients, 20 males and 2 females, aged 64±12, before emergency percutaneous coronary intervention (PCI), and 12 hours and 24 hours after-intervention, and measure the plasma IL-1β of 8 healthy controls, 6 males and 2 females, aged 56±9. (2) Forty rabbits underwent ligation of the left circumflex branch of coronary artery (LCX) for 50 minutes and reperfusion for 4 hours after the ligatures were untied. The rabbits were randomly divided into 4 groups of 10 rabbits to be injected into the left ventricle immediately before the reperfusion with rhIL-1ra 10 mg/kg (group A), 20 mg/kg (group B), or 40 mg/kg (group C), and normal saline (control group) respectively. After reperfusion of 4 hours, the LCX was re-ligated. Evans blue was injected into the left ventricle. 15% KCl was injected intravenously to kill the rabbits. Their hearts were taken out to weigh the non-ischemic, ischemic, and necrotic cardiac muscles so as to calculate the infarct size. The myoperoxidase (MPO) activity was measured by colorimetry. Sections of myocardium were made. The number of apoptotic cardiomyocytes was evaluated by TUNEL method. The apoptotic rate of cardiomyocyte was measured by annexin V method. The DNA expression of myocardium was detected by DNA laddering method. The expressions of Bcl-2 and Bax apoptosis genes were assessed. Results (1) The average plasma IL-1β level of the 22 AMI patients before emergency PCI was significantly higher than that of the controls (28 pg/ml±9 pg/ml vs. 20 pg/ml±11 pg/ml, P <0.05), and became the highest 12 hours after the intervention (86 pg/ml±14 pg/ml), and the high leve

关 键 词：白细胞介素-1受体拮抗剂 缺血再灌注 心肌损伤 ELISA法 经皮冠脉介入治疗 炎症反应 脱噬作用 

分 类 号：R542.22[医药卫生—心血管疾病]