目的应用大鼠在体心肌梗死后心室重构模型,探讨不同时间段重组人促红细胞生成素(recombinanthumanerythropoietin,rHu-EPO)对心肌梗死大鼠血流动力学、心功能及左室梗死面积的影响.探讨EPO抑制心肌梗死后心脏重构的给药时机和方案,为临床应用提供实验依据.方法选取健康SD大鼠60只,随机分为假手术组、单纯心肌梗死后心脏重构组、不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)各5只.在冠状动脉前降支的上1/3点以上处穿线结扎,制作心肌梗死模型,喂养4周.不同药物干预组在缺血开始前皮下注射药物,以后每周2次.分别于术后24h、2周、4周测定血流动力学参数,记录左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室内压最大上升速率(+dpMt)和左室内压最大下降速率(-dp/dt),并记录同步心率(HR).4周后处死动物收集心脏标本,根据左右心室实际重量(Lvw、Rvw),计算左右心室相对重量(LV/BW、RV/BW).Trc及伊文式蓝染色检测左室梗死面积、病理检测大体和镜下形态学改变.结果术后24h:与假手术组相比,单纯心肌梗死后心脏重构组左室收缩压(LVSP)、左室舒张末期压(LVEDP)和左室内压最大上升和下降速率(4-dp/dt)明显异常,LVSP、±dp/dt均显著降低,LVEDP显著升高(P〈0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dp/dt有明显改善(P〈0.05).术后2周:与假手术组相比,单纯心肌梗死后心脏重构组LVSP、LVEDP和4-dp/dt显著恶化(P〈0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dpMt有显著改善(P〈0.05).术后4周:与假手术组相比,单纯心肌梗死后心脏重构组LVSP、LVEDP和4-d
Objective Ventricular remodeling mode after myocardial infarction in rats was used to investigate the effects of recombinant human erythropoietin (rHu-EPO) on hemodynamic, ventricular function and infarct size of left ventricle in rats with myocardial infarction, so as to find out the optimum time and protocol of EPO treatment for ventricular remodeling after myocardial infarction and provide evidence for clinical application of EPO. Methods Sixty healthy male Sprague Dawley rats were divided randomly and equally into 5 groups: sham group, simple cardiacremodeling after myocardial infarction group, the intervention groups of different drugs (rHu-EPO in the intervention group and SB203580 group, rHu-EPO + SB203580, group) . Ligation was set at more than 1/3 points on the anterior descending coronary artery tO make model of myocardial infarction in rats, and the rats were feeded for four weeks. Different drugs in the intervention groups were subcutaneously injected once before ischemia and twice a week after ischemia. Respectively, 24 hours, 2 weeks, and 4 weeks after ischemia, we detected the hemodynamic parameters, recorded the left ventrieular systolic pressure (LVSP) , left ventricular end diastolic pressure (LVEDP) , maximal rate of left ventricular pressure (+ dp/dt) and left ventricular pressure decline rate (-dpMt) , and recorded the synchronization of heart rate (HR) . The animals were sacrificed 4 weeks after ischemia, and the heart specimens were collected. The relative weight of left and right ventricle (LV/BW in the RV/BW) was calculated according to the left and right ventricular weight (LVW, RVW) . TTC and Evans blue staining was used to detect left ventricular infarct size, and pathological examination was used to observe the gross and microscopic morphological change. Results 24 hours after operation: Compared with the sham group, in simply cardiac remodeling after myocardial infarction group, rats' left ventricular systolic pressure (LVSP) , left v