重组人促红细胞生成素预处理对缺血再灌注大鼠心肌保护作用的研究  

Cardioprotection of recombinant human erythropoietin pretreatmcnt on ischemia-repcrfused hearts and mechanism thereof:experiment with rats

作　　者：刘晓明[1] 贾真[2] 周志强[3] 徐建国[3] 

机构地区：[1]上海交通大学医学院附属新华医院麻醉科,200092 [2]武警河南总队医院麻醉科 [3]南京军区南京总医院麻醉科

出　　处：《中华医学杂志》2007年第35期2463-2467,共5页National Medical Journal of China

摘　　要：目的研究重组人促红细胞生成素(rhEPO)预处理对缺血再灌注(I-R)大鼠心肌的保护作用并谈讨其中可能的机制。方法雄性 Sprague-Dawley 大鼠共156只,I-R 模型采用阻断左前降支30 min 后再通3 h,大鼠于24 h 前分别腹腔注射生理盐水或 rhEPO。结束时测定心肌梗死面积和血浆心肌型肌酸激酶同功酸(CK-MB)水平,观察心肌组织超微结构改变和中性粒细胞浸润情况;酶联免疫吸附试验分别测定再灌注1 h 和2 h 时心肌肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的含量;凝胶电迁移方法检测心肌核因子-κB(NF-κB)和活化蛋白-1(AP-1)的表达。结果 I-R 前24 h 单次注射 rhEPO(静脉滴注,5000 U/kg)能显著降低 I-R 后心肌梗死面积,改善心肌细胞超微结构,削弱血浆 CK-MB 的水平,减轻心肌组织中中性粒细胞的浸润,降低 NF-κB和 AP-1的激活以及TNF-α和 IL-6的表达。结论 rhEPO 预处理有显著的心肌保护作用,该作用可能与抑制 NF-κB和AP-1的活化及下调下游促炎细胞因子有关。Objective To study the cardioprotective effects of recombinant human erythropoietin （rhEPO） on heart with ischemia-reperfusion （I-R） injury and the possible mechanism. Methods 156 SD rats, except 36 in the sham operation group, underwent ligation of the left descending coronary artery for 30 minutes and then reperfusion for 3 hours. 108 rats were randomly divided into 3 equal groups IR ± rhEPO group （ Group C, intraperitoneally injected with rhEPO 5000 U/kg 24 h before IR insult）, IR group （ Group B） , and sham-operation group （ Group A）. By the end of reperfusion blood sample were collected by cardiac puncture to detect the plasma content of MB isoenzyme of creatine kinase （CK-MB）. Before ischemia, after ischemia, and 30, 60, 120, and 180 min after reperfusion the hearts of 6 rats from each group were killed respectively with their hearts taken out. Another 12 rats were randomly divided into Groups B and C as described above to undergo IR insult, and underwent re-ligation, intravenous injection of Evans blue and pathological examination to observe the area of infarct size. Another 18 rats were divided into 3 equal groups： Groups A, B, and C as described above, and then underwent electron microscopy to observe the ultrastructure of the myocardium. Furthermore, another 18 rats were divided into3 equal groups： Groups A, B, and C as described above to undergo pathological examination of the heart and neutrophil infiltration. Tumor necrosis-alpha （TNF-α） and interleukin-6 （IL-6） concentrations of left ventricle were analyzed by ELISA 1 h and 2 h after reperfusion respectively; and nuclear factor-kappa B （NF-κB） and activator protein-1（AP-1） levels were detected by electrophoretic mobility shift assay. Results The ratio of infarct size to area at risk （IS%） of Group C was （28.0%±1.3%） , significantly lower than that of Group B [ （43.3 ± 2. 5 ） % , P 〈0. 01 ]. The plasma CK-MB concentrations of Groups B and C were （ 2110 ± 245 ） U/L and （ 1689 ± 138

关 键 词：缺血预处理 心肌 红细胞生成素 核因子-ΚB 活化蛋白-1 

分 类 号：R96[医药卫生—药理学]