AS、GS和PNS诱导MSCs分化为心肌样细胞的研究

发布时间：2018-12-12 15:41

【摘要】：心肌梗死后存活的心肌减少、继发心室重构,是造成心肌梗死患者发生心力衰竭、心律失常甚至死亡的重要原因,由于心肌细胞不能再生,损害的心肌细胞不能修复和分化,因此临床中药或西药治疗、介入治疗和手术治疗均不能代替坏死的心肌,而心脏移植由于手术复杂、供体困难和费用高等原因,在临床很难推广。因此,寻找可代替死亡细胞的移植物来防治心肌梗死后心衰、心肌重构,改善心功能是近年来研究的重要课题。近年的研究发现,骨髓基质中还存在另一类干细胞称之为骨髓间充质干细胞(mesenchymal stem cells,MSCs),在一定的环境和刺激因子作用下可分化为多种组织细胞,在组织工程中,MSCs作为一种重要的种子细胞越来越引起人们的关注,将MSCs诱导分化为心肌细胞移植治疗心肌梗死,为中药与干细胞结合治疗心血管疾病提供新的理论依据。 1、理论研究 MSCs属于非造血细胞,其基本特点是贴壁生长,呈纺锤状的纤维细胞样形态,国内外研究认为MSCs具有独特的表征和巨大的培养增殖能力,并且认为MSCs是多向分化潜能的干细胞,在一定条件下可以分化为骨骼、软骨、肌肉、神经和造血微环境组织等,具有很高的可塑性。国内外学者在体外培养中将MSCs经细胞传代后用5-氮胞苷(5-azacytidine,5-aza)对其进行诱导分化,可见有心肌细胞样超微结构,有心肌特异性基因表达,并有持续的动作电位,表明他们成功地诱导出心肌细胞。另有学者将MSCs直接注入自体心肌组织内,发现有心肌样细胞形成,具有肌钙蛋白T和肌球蛋白重链染色阳性的心肌细胞特异性标志,表明MSCs在体内微环境条件下可以诱导分化为心肌细胞近年来,有研究证明中药能有效地诱导MSCs分化为神经元细胞和成骨细胞,并且诱导率高。由于MSCs的可塑性大,在某种条件下可以分化为包括心肌细胞在内的多种功能细胞,而应用中药成功诱导MSCs分化为神经元样细胞和成骨细胞的研究结果提示我们,在理论上可以相信某些中药有可能诱导MSCs分化为心肌细胞。目前国内外对中药能否诱导MSCs分化为心肌细胞的研究还报道甚少,所以我们在众多的中药中,筛选临床上常用治疗冠心病的药物,如黄芪、人参、三七
[Abstract]:The decrease of surviving myocardium and the secondary ventricular remodeling after myocardial infarction are the important causes of heart failure, arrhythmia and even death in patients with myocardial infarction. The damaged cardiomyocytes can not be repaired and differentiated because the myocardial cells can not regenerate. Therefore, clinical Chinese medicine or western medicine treatment, interventional therapy and surgical treatment can not replace the necrotic myocardium, and heart transplantation is difficult to be popularized in clinic because of complicated operation, difficult donor and high cost. Therefore, it is an important research topic in recent years to search for grafts that can replace dead cells to prevent heart failure, myocardial remodeling and improve cardiac function after myocardial infarction. In recent years, it has been found that there is another kind of stem cells in bone marrow stromal cells, called (mesenchymal stem cells,MSCs), which can differentiate into many kinds of tissue cells under the action of certain environment and stimulant factors, and in tissue engineering, MSCs, as an important seed cell, has attracted more and more attention. The differentiation of MSCs into cardiomyocytes in the treatment of myocardial infarction provides a new theoretical basis for the combination of traditional Chinese medicine and stem cells in the treatment of cardiovascular disease. 1. MSCs is a non-hematopoietic cell, which is characterized by adherent growth and fusiform fibrous morphology. Domestic and foreign studies have shown that MSCs has a unique characterization and great ability to culture and proliferate. It is considered that MSCs is a multipotential stem cell, which can differentiate into bone, cartilage, muscle, nerve and hematopoietic microenvironment under certain conditions, and has high plasticity. MSCs was induced to differentiate by 5-azacytidine 5-aza after subculture in vitro by domestic and foreign scholars. It was found that there were cardiomyocyte-like ultrastructure, myocardial specific gene expression and continuous action potential. This suggests that they successfully induced cardiomyocytes. Other researchers injected MSCs directly into autologous myocardial tissue and found that there were cardiomyocyte like cells formed, which had specific markers of cardiac troponin T and myosin heavy chain staining. It is suggested that MSCs can induce cardiomyocyte differentiation under microenvironment in vivo. In recent years, it has been proved that Chinese herbal medicine can effectively induce MSCs to differentiate into neuronal cells and osteoblasts, and the induction rate is high. Because of the large plasticity of MSCs, it can be differentiated into many kinds of functional cells, including cardiomyocytes, under certain conditions. However, the successful application of Chinese medicine in inducing MSCs to differentiate into neuron-like cells and osteoblasts suggests that we can differentiate into neuron-like cells and osteoblasts. In theory, it is believed that some Chinese herbs may induce MSCs to differentiate into cardiomyocytes. There are few reports at home and abroad on whether traditional Chinese medicine can induce MSCs differentiation into cardiomyocytes. Therefore, we screen the commonly used drugs for coronary heart disease, such as astragalus, ginseng, Panax notoginseng, among many Chinese medicines, such as Astragalus membranaceus, Panax ginseng and Panax notoginseng.
【学位授予单位】：广州中医药大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R329

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