【摘要】：心肌梗死后存活的心肌減少、繼發(fā)心室重構(gòu),是造成心肌梗死患者發(fā)生心力衰竭、心律失常甚至死亡的重要原因,由于心肌細(xì)胞不能再生,損害的心肌細(xì)胞不能修復(fù)和分化,因此臨床中藥或西藥治療、介入治療和手術(shù)治療均不能代替壞死的心肌,而心臟移植由于手術(shù)復(fù)雜、供體困難和費(fèi)用高等原因,在臨床很難推廣。因此,尋找可代替死亡細(xì)胞的移植物來(lái)防治心肌梗死后心衰、心肌重構(gòu),改善心功能是近年來(lái)研究的重要課題。近年的研究發(fā)現(xiàn),骨髓基質(zhì)中還存在另一類(lèi)干細(xì)胞稱(chēng)之為骨髓間充質(zhì)干細(xì)胞(mesenchymal stem cells,MSCs),在一定的環(huán)境和刺激因子作用下可分化為多種組織細(xì)胞,在組織工程中,MSCs作為一種重要的種子細(xì)胞越來(lái)越引起人們的關(guān)注,將MSCs誘導(dǎo)分化為心肌細(xì)胞移植治療心肌梗死,為中藥與干細(xì)胞結(jié)合治療心血管疾病提供新的理論依據(jù)。 1、理論研究 MSCs屬于非造血細(xì)胞,其基本特點(diǎn)是貼壁生長(zhǎng),呈紡錘狀的纖維細(xì)胞樣形態(tài),國(guó)內(nèi)外研究認(rèn)為MSCs具有獨(dú)特的表征和巨大的培養(yǎng)增殖能力,并且認(rèn)為MSCs是多向分化潛能的干細(xì)胞,在一定條件下可以分化為骨骼、軟骨、肌肉、神經(jīng)和造血微環(huán)境組織等,具有很高的可塑性。國(guó)內(nèi)外學(xué)者在體外培養(yǎng)中將MSCs經(jīng)細(xì)胞傳代后用5-氮胞苷(5-azacytidine,5-aza)對(duì)其進(jìn)行誘導(dǎo)分化,可見(jiàn)有心肌細(xì)胞樣超微結(jié)構(gòu),有心肌特異性基因表達(dá),并有持續(xù)的動(dòng)作電位,表明他們成功地誘導(dǎo)出心肌細(xì)胞。另有學(xué)者將MSCs直接注入自體心肌組織內(nèi),發(fā)現(xiàn)有心肌樣細(xì)胞形成,具有肌鈣蛋白T和肌球蛋白重鏈染色陽(yáng)性的心肌細(xì)胞特異性標(biāo)志,表明MSCs在體內(nèi)微環(huán)境條件下可以誘導(dǎo)分化為心肌細(xì)胞 近年來(lái),有研究證明中藥能有效地誘導(dǎo)MSCs分化為神經(jīng)元細(xì)胞和成骨細(xì)胞,并且誘導(dǎo)率高。 由于MSCs的可塑性大,在某種條件下可以分化為包括心肌細(xì)胞在內(nèi)的多種功能細(xì)胞,而應(yīng)用中藥成功誘導(dǎo)MSCs分化為神經(jīng)元樣細(xì)胞和成骨細(xì)胞的研究結(jié)果提示我們,在理論上可以相信某些中藥有可能誘導(dǎo)MSCs分化為心肌細(xì)胞。 目前國(guó)內(nèi)外對(duì)中藥能否誘導(dǎo)MSCs分化為心肌細(xì)胞的研究還報(bào)道甚少,所以我們?cè)诒姸嗟闹兴幹?篩選臨床上常用治療冠心病的藥物,如黃芪、人參、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.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類(lèi)號(hào)】：R329

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