利用小鼠心脏移植模型研究心梗后心肌再生的细胞来源及相关机制

项目名称： 利用小鼠心脏移植模型研究心梗后心肌再生的细胞来源及相关机制

项目编号： No.81460050

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 蒋智

作者单位： 贵州省人民医院

项目金额： 47万元

中文摘要： 近年来发现哺乳动物心脏在正常衰老和疾病状态下均有心肌再生现象。有研究表明新生心肌细胞可能主要来源于心肌干细胞增殖分化，也有研究严重质疑心肌干细胞的心肌修复能力。我们认为造成上述分歧的关键在于目前的研究方法及动物模型的不足以及受多种因素的干扰，不能可靠的评估新生心肌细胞的来源和数量。因此，我们在前期研究中首先对雌性野生型小鼠造成心肌缺血再灌注损伤，然后将损伤心脏移植给雄性GFP小鼠，建立急性心肌缺血再灌注损伤后心脏移植模型，移植心脏中GFP阳性纯Y染色体阳性的单核/多核心肌细胞可明确为宿主干细胞来源的新生心肌细胞。该动物模型国内外尚无报道，我们将以此为基础，采用免疫荧光、流式细胞、膜片钳等技术，从整体-细胞两个层次，通过观察宿主干细胞来源心肌细胞数量、功能以及对不同趋化因子的反应，揭示衰老及心肌损伤情况下干细胞来源心肌再生的规律、有关的干细胞类型及可能的调控机制。

中文关键词： 心肌梗死；心肌细胞；心脏干细胞；心脏移植；心肌再生

英文摘要： Recent evidence suggests that the mammalian heart has intrinsic regenerative potential. Two diametrically opposed views have emerged as to whether a population of stem cell contributes to heart regeneration by forming new myocytes. We consider that the disadvantage of the research methods and animal model, which is insufficient to recognize newly formed myocytes, is the key reason that lead to the controvercy. Here, we first induce ischemic reperfusion damage to the heart of a wild type female mouse, and then transplant the heart to a GFP male mouse to establish a mouse model of injured heart transplantation. After a period of self-repair, the GFP+/Y chromosome+ mononuclear or multinuclear myocytes in the graft are defined as newly formed myocytes derived from host stem cells. The mouse model has not been reported. Based on this, we will evaluate the number, function and response to chemokines of the host derived stem cells by using immunofluorescent imaging, flow cytomety and patch clamp. We will reveal how the stem cells excel regenerate the heart, but also provide a more reliable mouse model to study stem-cell-based cardiac regeneration.

英文关键词： myocardial infarction;cardiomyocyte;cardiac stem cell;heart transplantation;myocardial regeneration