氨氯地平对急性心肌梗死大鼠血管新生和心功能的影响
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国家自然科学基金(81070195、81000055);江苏省自然基金(BK2010107)


Effects of Amlodipine on Neovascularization and Cardiac Function in Rats after Acute Myocardial Infarction
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    目的 观察氨氯地平对大鼠急性心肌梗死后血管新生及心功能的影响,并探讨其可能的机制。方法 结扎冠状动脉左前降支制造雄性Sprague-Dawley大鼠急性心肌梗死模型。术后将大鼠随机分为氨氯地平治疗组和对照组,每组20只。CD31和α-平滑肌肌动蛋白免疫荧光染色法分别评估急性心肌梗死14天后心肌梗死周围区微血管及心肌小动脉新生情况。流式细胞术检测术前及术后7天外周血CD45-/low+CD133+KDR+内皮祖细胞数量。免疫印迹法测定治疗14天心肌梗死周围区血管新生相关通路蛋白的表达。超声心动图评估心功能改变。结果 氨氯地平治疗可明显促进急性心肌梗死后心肌微血管(81.3±4.0比69.0±5.6,P<0.05)和小动脉(11.5±3.5比6.2±2.3,P<0.05)新生,同时伴有循环中内皮祖细胞数量 (120.3±18.3/106单核细胞比42.5±6.3/106单核细胞,P<0.01) 增加,心肌梗死周围区血管新生相关通路的信号分子,如血管内皮生长因子、磷酸化蛋白激酶B、磷酸化内皮型一氧化氮合酶的表达增加,一氧化氮释放增多(P<0.05)。与对照组相比,治疗后大鼠左心室射血分数和左心室缩短分数明显改善(P<0.01),左心室收缩期末内径减小(P<0.05)。结论 氨氯地平能增加心肌梗死后血管新生,并改善心肌梗死后心功能。这种作用可能通过增加循环中内皮祖细胞数量以及活化心肌血管新生相关通路介导。

    Abstract:

    Aim To investigate the beneficial effects of amlodipine on neovascularization and cardiac function in rats after acute myocardial infarction (AMI), and explore the potential underlying mechanism for these effects. Methods Left anterior descending coronary artery ligation was performed to induce AMI. Rats post-AMI were randomly assigned into amlodipine group and control group after surgery (n20 in each group). Capillary density in the peripheral area of infarction and small artery density in myocardium were determined by CD31 and α-SMA staining separately. The percentage of CD45-/low+CD133+KDR+ EPC in peripheral blood mononuclear cells was measured by flow cytometry pre-operation and on day 7 post-operation. The expression and phosphorylation of protein associated with neovascularization in the border zone of infarction were determined by Western blot analysis. Echocardiagraphy was performed to evaluate cardiac function. Results Amlodipine treatment could notably increase the density of capillary vessels (81.3±4.0 vs 69.0±5.6, P<0.05) around infarction and small arteries (11.5±3.5 vs 6.2±2.3, P<0.05) in myocardium. At the same time, elevated circulating EPC count (120.3±18.3/106 vs 42.5±6.3/106, P<0.01) as well as increased expression of VEGF, phosphor-Akt, phosphor-eNOS and NO in the border zone of infarction (all P<0.05) were observed.

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孙佳音,翟 琳,李巧玲,康丽娜,徐 标.氨氯地平对急性心肌梗死大鼠血管新生和心功能的影响[J].中国动脉硬化杂志,2013,21(07):589~593.

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  • 收稿日期:2013-01-22
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