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重组人红细胞生成素对大鼠急性心肌梗死的影响

Protective effect of recombinant human erythropoietin against acute myocardial infarction in rats

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【作者】 张郁青张馥敏张定国周蕾姚静陈亦江常在高翔李传富哈团柱马文珠曹克将

【Author】 ZHANG Yu-Qing1, ZHANG Fu-Min1, ZHANG Ding-Guo1, ZHOU Lei1, YAO Jing1, CHEN Yi-Jiang1, CHANG Zai2, GAO Xiang2, LI Chuan-Fu3, HA Tuan-Zhu3, MA Wen-Zhu1, CAO Ke-Jiang11Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China, 2Animal Model Center, Nanjing University, Nanjing 210000,China, 3Department of Surgery, East Tennessee State University,Johnson City,TN,37614,USA

【机构】 南京医科大学第一附属医院心脏科南京大学模式动物中心美国田纳西州大学外科学系南京医科大学第一附属医院心脏科 江苏南京210029江苏南京210029江苏南京210000Johnson CityTN37614

【摘要】 目的:观察重组人红细胞生成素(rHuEPO)对心肌梗死大鼠心功能和心肌梗死面积的影响,并探讨其机制.方法:16只Wistar大鼠随机分心肌梗死组和治疗组,结扎左冠前降支制备急性心肌梗死模型,治疗组围手术期连续3d腹腔注射rHuEPO[3000IU/(kg·d)],14d后以相同剂量再连续注射3d;术后2d及3wk二维超声心动图检查心功能;术后3wk处死大鼠,TTC测定心肌梗死面积,免疫组化检测缺血区毛细血管密度、Bcl2和Bax的表达.结果:术后2d两组之间心功能无明显差异,术后3wk对照组左室射血分数(LVEF)和左室收缩末期内径(LVDs)改善程度明显劣于治疗组(P<0.05).与对照组相比,术后3wk治疗组梗死面积明显减少[分别为(26.0±0.9)%,(28.1±1.5)%,P<0.05]、毛细血管密度显著增加[分别为(10.4±1.5)/视野,(6.3±0.7)/视野,P<0.05],Bcl2蛋白表达增加(A值分别为0.116±0.005,0.103±0.007,P<0.05),而Bax表达减弱(A值分别为0.125±0.010,0.147±0.014,P<0.05).结论:rHuEPO能缩小大鼠心肌梗死面积,改善心肌梗死后心功能,其机制可能与减少缺血区心肌细胞凋亡以及促进缺血区毛细血管生成有关.

【Abstract】 AIM: To study the protective effects of recombinant human erythropoietin (rHuEPO) on heart function and infarct size in rats with acute myocardial infarction (AMI) and to explore the mechanism of the protective effect. METHODS: Sixteen Wistar rats were divided randomly into 2 groups: AMI group (n=8) and treatment group (n=8). AMI models were made by ligating the left anterior descending coronary artery(LAD). rhEPO was injected in treatment group (3000 IU/ kg, ip) once daily for 3 conse- cutive days (1 d before, at the start of, and 1 d after surgery) and 2 wk later (14-16 d after surgery). Transthoracic echocardiography was carried out 2 and 21 d after operation respectively. Then the rats were sacrificed. Infarct sizes were measured by TTC stain, vascular density and the expressions of Bcl-2 and Bax examined by immunohistochemical technique. RESULTS: There was no significant difference in baseline LV functions between AMI group and treatment group 2 d after operation. LVEF and LVDs were significantly improved in treatment group than those in AMI group on 21 d after operation. Also,the smaller infracted size [(26.0±0.9)% vs (28.1±1.5)%, P<0.05], and higher capillary density[(10.4±1.5)/scope vs (6.3±0.7)/scope, P<0.05] were confirmed in treatment group than those in AMI group on 21 d after operation. An up- regulation of Bcl-2 A value [(0.116±0.005) vs (0.103± 0.006), P<0.05] and a down-regulation of Bax A value [ (0.125±0.010) vs (0.147± 0.014), P<0.05 ] were found in treatment group as compared with those of AMI group. CONCLUSION: RHuEPO could improve rats heart function and reduce infarct size after myocardial infarction, which may be related with reducing apoptosis and stimulating angiogenesis.

【基金】 江苏省科技厅重大项目(BK2002208)
  • 【文献出处】 第四军医大学学报 ,Journal of the Fourth Military Medical University , 编辑部邮箱 ,2006年07期
  • 【分类号】R542.22
  • 【被引频次】4
  • 【下载频次】95
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