microRNA-503在糖尿病大鼠心肌梗死后血管新生过程中的变化
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福建省自然科学基金青年项目(2012J015146);高等学校博士学科点专项科研基金资助课题新教师类基金(20113518120006)


MicroRNA-503 Contributes to Diabetes Mellitus Induced Impairment Reparative Angiogenesis After Acute Myocardial Infarction
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    摘要:

    目的 通过比较自发糖尿病GK大鼠与Wistar大鼠急性心肌梗死后,梗死边缘区心肌组织内血管新生水平、microRNA-503(miR-503)及其靶基因水平的变化,探讨miR-503在糖尿病心肌缺血后血管新生中的调控作用。方法 选取GK大鼠、Wistar大鼠各30只,结扎左前降支近段建立急性心肌梗死模型,分别于术前及术后3天、7天、14天、28天处死动物,留取血浆及心脏组织。免疫组织化学染色法检测梗死边缘区心肌Ⅷ因子表达计数微血管数;qRT-PCR检测组织中miR-503水平;Western blot检测梗死边缘区细胞周期素E1和细胞分裂周期蛋白25A表达水平。结果 在缺血后各时间点,GK大鼠组心肌梗死边缘区微血管数量均少于Wistar大鼠组(P<0.05),而心肌组织内的miR-503水平均高于Wistar大鼠组(P<0.05),细胞分裂周期蛋白25A表达水平均低于Wistar大鼠组(P<0.05)。GK大鼠组心肌组织细胞周期素E1蛋白表达水平仅在术后14天及28天时低于Wistar大鼠组(P<0.05)。结论 糖尿病可引起心肌缺血组织边缘区miR-503异常升高;升高的miR-503可能通过抑制细胞分裂周期蛋白25A的表达,参与调控糖尿病心肌梗死边缘区组织内血管新生能力的下降。

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    Aim To explore the expression of micorRNA-503 and its target genes,in process of diabetes mellitus induced impairment reparative angiogenesis after acute myocardial infarction. Methods GK rats and Wistar rats 30 each were made into the model of acute myocardial infarction by ligating the left anterior descending coronary artery. Capillary density around the region of infarction was detected by immunohistochemical staining with vWF,expression of micorRNA-503 was measured by qRT-PCR,and the protein expressions of cyclinE1 and cell division cycle 25A (CDC25A) were measured by Western blot. Analysis of cappilaries,micorRNA-503,cyclinE1 and CDC25A were made on days 0(pre-ligation),3,7,14 and 28 days post-ligation. Results In each time point post-ligation,the capillary density around the region of infarction and expression of CDC25A decreased in GK rats compared with Wistar rats,the expression of micorRNA-503 increased significantly (P<0.05). Decreased expression of cyclinE1 in GK rats was only observed on 14 and 28 days post-ligation (P<0.05). Conclusion Our data suggest that micorRNA-503 contribute to diabetes mellitus induced impairment reparative angiogenesis after acute myocardial infarction,via down-regulation of CDC25A.

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陈 琴,黄铭涵,张在保,郑行春. microRNA-503在糖尿病大鼠心肌梗死后血管新生过程中的变化[J].中国动脉硬化杂志,2015,23(03):261~265.

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  • 收稿日期:2014-12-01
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