培哚普利改善糖尿病大鼠急性心肌梗死后内皮祖细胞动员
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国家自然科学基金(81070195,81000055)和江苏省自然科学基金(BK 2010107)


Perindopril Improves Endothelial Progenitor Cell Mobilization in Diabetic Rats After Acute Myocardial Infarction
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    摘要:

    目的 观察培哚普利对糖尿病大鼠急性心肌梗死后骨髓内皮祖细胞动员和血管新生障碍的影响,并探讨其可能的分子机制。方法 高脂饮食联合小剂量链脲霉素诱导雄性SD大鼠糖尿病模型,成模4周后结扎冠状动脉左前降支造成急性心肌梗死模型。术后将大鼠随机分至培哚普利治疗组和模型组(各组n15)。流式细胞术检测术前及术后不同时间点(1、3、5、7、14和28天)外周血CD45-/low+CD133+KDR+内皮祖细胞数量,ELISA法检测不同时间点血浆血管内皮生长因子水平。CD31免疫荧光染色法评估心肌梗死1个月后心肌梗死周围区血管新生情况。超声心动图评估心功能改变。免疫印迹法测定骨髓细胞中内皮祖细胞动员相关通路蛋白的表达。结果 培哚普利治疗可显著改善糖尿病时缺血诱导的内皮祖细胞动员障碍,使循环内皮祖细胞峰值明显升高(103±37个/106单核细胞比58±19个/106单核细胞,P<0.05),同时伴有血浆血管内皮生长因子水平升高,骨髓内皮祖细胞动员通路的信号分子蛋白激酶B与内皮型一氧化氮合酶磷酸化增加以及基质金属蛋白酶9 的表达升高(P<0.05)。与模型组相比,培哚普利治疗后糖尿病大鼠心肌梗死周围区新生毛细血管密度显著增加,射血分数及左心室短轴缩短率明显改善(所有P<0.05)。结论 培哚普利能改善糖尿病大鼠缺血诱导的骨髓内皮祖细胞动员障碍,增加缺血区血管新生,最终改善心功能。这种作用可能通过活化骨髓内皮祖细胞动员相关通路介导。

    Abstract:

    Aim To investigate the beneficial effects of perindopril on bone marrow-endothelial progenitor cell (EPC) mobilization, neovascularization and cardiac function in diabetic rats after acute myocardial infarction (AMI), and explore the potential underling mechanism for these effects. Methods High fat diet combined with a low dose of Streptozocin (STZ) was used to induce diabetic models, then left anterior descending coronary artery ligation was performed to induce AMI. Diabetic rats were randomly assigned into perindopril group or control group after surgery (n15 in each group). The percentage of CD45-/low+CD133+KDR+EPC in peripheral blood mononuclear cells was measured by flow cytometry pre-operation and at day1,3,5,7,14,28 post-operation, and the plasma level of vascular endothelial growth factor (VEGF) at the same time points was measured by enzyme linked immunosorbent assay (ELISA) kit. Capillary density in the peripheral area of infarction was determined by CD31 staining. Echocardiagraphy was performed to evaluate cardiac function. The expression and phosphorylation of protein associated with EPC mobilization in bone marrow were determined by Western blot analysis. Results Perindopril treatment could notably improve the impaired ischemia-induced EPC mobilization in diabetic condition, and elevate the tiptop of circulating EPC (103±37/106 vs 58±19/106, P<0.05). At the same time, the level of plasma VEGF was raised, the expression of Akt and endothelial nitric oxide synthase (eNOS)

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孙佳音,康丽娜,徐 标.培哚普利改善糖尿病大鼠急性心肌梗死后内皮祖细胞动员[J].中国动脉硬化杂志,2013,21(06):481~485.

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  • 收稿日期:2013-01-04
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