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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。
OBJECTIVE: To study the effect of recombinant human erythropoietin on acute myocardial infarction (AMI) in rats and its effects on the changes of apoptosis and the changes of capillary density and cardiac function in ischemic area. Methods: The experiment was performed at Model Animal Research Institute of Nanjing University from June 2004 to June 2005. Sixteen healthy male Wistar rats were randomly divided into acute myocardial infarction group, recombinant human erythropoietin group, 8 / group. ① Both groups were ligated with the left anterior descending coronary artery to establish the model of acute myocardial infarction, local myocardial purple, wall bulging model for the successful signs. ② Recombinant human erythropoietin group was intraperitoneally injected with recombinant human erythropoietin 3000IU / kg intraperitoneally daily for 3 days (ie, on the first day of surgery, on the day of surgery, and on the first day of surgery), and on the 14th, 15th and 16th day after operation, The dose is injected continuously for 3 days. Acute myocardial infarction group were given equal amount of saline at various time points after operation. The left ventricular anterior descending coronary artery ligation 3 weeks after the end of the determination of the ischemic capillary density, Bcl-2 and Bax levels, 2d and 3weeks using two-dimensional echocardiography two groups of rat heart chamber structure and cardiac function. Results: Sixteen rats were selected in the experiment and all were involved in the result analysis. ①Three weeks after operation, capillary density measurement results showed that capillary density of recombinant human erythropoietin group increased significantly (± 10.4 ± 1.5), (6.3 ± 0.7) / visual field, P <0.05 compared with acute myocardial infarction group犦. ② The expression of Bcl-2 and Bax proteins in the myocardial tissue of the three groups at the end of the third week: Compared with the acute myocardial infarction group, the Bax expression in the recombinant human erythropoietin group was significantly weaker (0.1465 ± 0.0138), (0.1248 ± 0.0098) A, P <0.05 犦, while the expression of Bcl-2 was significantly increased 犤 (0.1030 ± 0.0056), (0.1163 ± 0.0050) A, P <0.05 犦. ③ Changes of cardiac function at the end of 3 weeks after operation in both groups: Compared with acute myocardial infarction group, left ventricular end-diastolic diameter and left ventricular end-systolic diameter of recombinant human erythropoietin significantly decreased (6.25 ± 0.32), ( 5.51 ± 0.35) mm, (4.22 ± 0.21) and (3.45 ± 0.24) mm respectively; all P <0.05 犦, the left ventricular ejection fraction increased significantly (69.08 ± 2.23)% and (75.24 ± 3.64)%, P < 0.05 犦. Conclusion: Recombinant human erythropoietin can reduce the apoptosis of myocardial cells in ischemic area and promote the formation of capillary vessels in ischemic area, so as to improve and improve the cardiac function in myocardial infarction rats.