重组人红细胞生成素对大鼠急性心肌梗死区域及缺血区毛细血管密度的影响

Effect of recombinant human erythropoietin on capillary density in acute myocardial infarction region and ischemic region

目的:应用重组人红细胞生成素治疗大鼠急性心肌梗死,观察其对心肌梗死区域细胞凋亡以及缺血区毛细血管密度变化和心功能的影响。方法:实验于2004-06/2005-06在南京大学模式动物研究所完成。选取健康雄性Wistar大鼠16只,随机分为急性心肌梗死组、重组人红细胞生成素组,8只/组。①两组大鼠均结扎左冠前降支建立急性心肌梗死模型,局部心肌变紫色、室壁膨出为模型成功标志。②重组人红细胞生成素组围手术期每天腹腔注射重组人红细胞生成素3000IU/kg,共3d(即手术前1d、手术当天、手术后1d),在术后第14,15,16天以同等剂量再连续注射3d。急性心肌梗死组术后各时间点给予等量生理盐水。③左冠状动脉前降支结扎术后3周末测定缺血区毛细血管密度、Bcl-2和Bax的水平,2d及3周末采用二维超声心动图检查两组大鼠心腔结构及心功能。结果:实验选取大鼠16只,全部进入结果分析。①两组术后3周末毛细血管密度测量结果:与急性心肌梗死组比较,重组人红细胞生成素组毛细血管密度明显增加犤(10.4±1.5),(6.3±0.7)个/视野,P<0.05犦。②两组术后3周末心肌组织Bcl-2和Bax蛋白的表达:与急性心肌梗死组比较,重组人红细胞生成素组Bax表达明显减弱犤(0.1465±0.0138),(0.1248±0.0098)A,P<0.05犦,而Bcl-2表达则明显增强犤(0.1030±0.0056),(0.1163±0.0050)A,P<0.05犦。③两组术后3周末心功能各项指标的变化:与急性心肌梗死组比较,重组人红细胞生成素组左室舒张末期内径、左室收缩末期内径均显著降低犤(6.25±0.32),(5.51±0.35)mm;(4.22±0.21),(3.45±0.24)mm;P均<0.05犦,左室射血分数明显升高犤(69.08±2.23)%,(75.24±3.64)%,P<0.05犦。结论:重组人红细胞生成素能减少缺血区心肌细胞凋亡及促进缺血区毛细血管的生成,从而改善和提高心肌梗死大鼠的心脏功能。

AIM： Recombinant human erythropeietin is used to treat acute myocardial infarction of the rats, then to observe its effect on cellular apeptosis in the region of myocardial infarction as well as capillary density of ischemic region and cardiac function. METHODS： This experiment was conducted at the Research Institute of Model Animals of Nanjing University from June 2004 to June 2005. Totally 16 healthy male Wistar rats were chosen and randomly divided into acute myocardial infarction group （n=8） and recombinant human erythropeietin group （n=8）. ①Rat models were created by ligating the left anterior descending coronary artery （LAD） in the two groups, local myocardium was purple, and bulge of ventricular wall marked the model was successful. ② 3 000 IU/ kg recombinant human erythropeietin was intraperitoneally in- jected into the rats in the recombinant human erythropeietin group every day during perioperative period, 3 days in total （one day before operation, on the day of the operation, 1 day after operation）. Same volume of recombinant human erythropeietin was injected successively on postoperative days 14, 15 and 16. The rats in the acute myocardial infarction group were given the same volume of normal saline at each time point. ③After ligating LAD, capillary density, the level of Bcl-2 and Bax of ischemic region were determined at the end of the third week. Structure of cardiac cavity and cardiac function of the rats in the two groups were examined with two-dimensional echocardiogram on day 2 and at the end of the third week. RESULTS： All the 16 rats enrolled in the experiment entered the stage of result analysis. ①Measuring result of capillary density of the rats at the end of the third week after operation： capillary density of recombinant hu- man erythropeietin was obviously increased as compared with acute my- ocardial infarction group, [（10.4±1.5） vs （6.3±0.7）/field,P 〈 0.05].② Expression of Bcl-2 and Bax protein of cardiac tissue at the end of the third week after operation in the two groups ： As compared with acute myocardial infarction group, Bax expression of recombinant human erythropoietin was obviously decreased [（0.146 5±0.013 8）vs （0.1248±0.009 8） A ,P 〈 0.05],while Bcl-2 expression was obviously increased [（0.103 ±0.005 6）vs（0.116 3±0.005 0） A ,P 〈 0.05]. ③ Change of cardiac function and other indexes at the end of the third week after operation of the two groups： left ventricular diastolic diameter（LVEDD） and left ventricular end- diastolic diameter（LVESDD） of recombinant human erythropeietin group was all significantly decreased as compared with acute myocardial infarction group [（6.25±0.32）vs（5.51±0.35） mm;（4.22±0.21）vs（3.45±0.24） ram;both P 〈 0.05] ,while left ventrical ejection fraction was significantly increased [（69.08±2.23）% vs （75.24±3.64）% ,P 〈 0.05]. CONCLUSION： Recombinant human erythropeietin can reduce ventricular cellular apeptosis of isehemic region and promote vascularization of ischemic region , so as to improve and enhance cardiac function of myocardial infarction rats.