miRNA-15a/b调控心肌梗死区骨髓间充质干细胞的存活及促血管形成的分子成像研究

Nowadays, many researchers devote to studying myocardium regeneration and repairing insulted myocardium with stem cells. The experimental and preclinical studies showed that bone mesenchymal stem cells (BMSCs) have the ability of differentiating into cardiac myocytes, promoting angiogenesis, and improving haemodynamics in myocardial infarction area. However, it is difficult to achieve the desired results of BMSCs treatment for acute myocardial infarction because most of BMSCs are not able to adapt to hypoxia within the infarct zone and die in a very short period of time. How to improve the survival rate of BMSCs has become the key issue and must be solved before clinical applications. Recent studies have demonstrated that microRNAs (miRNAs) are crucial for normal BMSCs self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of BMSCs has not been clearly established. Till now, no studies focus on the role of miRNA-15a/b in anti-apoptosis and pro-angiogenesis effects of stem cells after heart transplantation. Our previous study demonstrated that knockdown of miR-15a/b in BMSCs could reduce BMSCs apoptosis via targeting Bcl-2 gene and promote the secretion of VEGF in hypoxic condition. So, we hypothesize that down-regulation of miR-15a/b in BMSCs plays an important role in the regulation of BMSCs survival and angiogenesis in myocardial infarction area. To confirm this hypothesis, we will establish a model of myocardial infarction in VEGFR2-Fluc transgenic mice and reveal the effects of miRNA-15a/b in BMSCs in treatment of acute myocardial infarction via the combination of molecular imaging techniques and molecule biological methods. It is reasonable to speculate that miRNA-15a/b, the novel but practical regulator of stem cell implantation for ischemic heart disease, introduces a promising strategy for the treatment of myocardial infarction.

目前，骨髓间充质干细胞（BMSCs)治疗心肌梗死已经成为心血管病学研究的热点之一。然而，大部分BMSCs由于无法适应梗死区缺氧环境而死亡，难以达到BMSCs治疗的预期效果。如何提高BMSCs的存活率已成为BMSCs 最终走向临床应用必须解决的难题。研究表明miRNAs在干细胞的自我更新和分化过程中发挥重要的调控作用。我们前期预实验结果证实抑制BMSCs中miR-15a/b表达，可上调BMSCs中Bcl-2及VEGF表达，提高BMSCs抗缺氧及增强VEGF分泌的能力。基于以上发现，我们推测miR-15a/b在心肌梗死区调控BMSCs存活及促血管形成方面发挥重要的作用。为证实这一假说，我们将建立VEGFR2-Fluc转基因鼠心肌梗死模型，采用分子影像学与分子生物学相结合的方法，从多角度、多层次揭示miR-15a/b在BMSCs治疗心肌梗死调控中的作用，为BMSCs治疗心肌梗死提供新的切入点。

目前，骨髓间充质干细胞（BMSCs)治疗心肌梗死已经成为心血管病学研究的热点之一。然而，大部分BMSCs 由于无法适应梗死区缺氧环境而死亡，难以达到BMSCs 治疗的预期效果。如何提高BMSCs 的存活率已成为BMSCs 最终走向临床应用必须解决的难题。研究表明 miRNAs 在干细胞的自我更新和分化过程中发挥重要的调控作用。我们前期预实验结果证实抑制BMSCs 中miR-15a/b 表达，可上调BMSCs 中Bcl-2 及VEGF 表达，提高BMSCs 抗缺氧及增强VEGF 分泌的能力。基于以上发现，我们推测miR-15a/b 在心肌梗死区调控BMSCs存活及促血管形成方面发挥重要的作用。为证实这一假说，我们将建立VEGFR2-Fluc 转基因鼠心肌梗死模型，采用分子影像学与分子生物学相结合的方法，从多角度，多层次揭示miR-15a/b 在BMSCs 治疗心肌梗死调控中的作用，为BMSCs 治疗心肌梗死提供新的切入点。