發(fā)布時間：2018-12-12 15:41

【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,由于心肌細胞不能再生,損害的心肌細胞不能修復(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、供體困難和費用高等原因,在臨床很難推廣。因此,尋找可代替死亡細胞的移植物來防治心肌梗死后心衰、心肌重構(gòu),改善心功能是近年來研究的重要課題。近年的研究發(fā)現(xiàn),骨髓基質(zhì)中還存在另一類干細胞稱之為骨髓間充質(zhì)干細胞(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胞,在組織工程中,MSCs作為一種重要的種子細胞越來越引起人們的關(guān)注,將MSCs誘導(dǎo)分化為心肌細胞移植治療心肌梗死,為中藥與干細胞結(jié)合治療心血管疾病提供新的理論依據(jù)。 1、理論研究 MSCs屬于非造血細胞,其基本特點是貼壁生長,呈紡錘狀的纖維細胞樣形態(tài),國內(nèi)外研究認為MSCs具有獨特的表征和巨大的培養(yǎng)增殖能力,并且認為MSCs是多向分化潛能的干細胞,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。國內(nèi)外學者在體外培養(yǎng)中將MSCs經(jīng)細胞傳代后用5-氮胞苷(5-azacytidine,5-aza)對其進行誘導(dǎo)分化,可見有心肌細胞樣超微結(jié)構(gòu),有心肌特異性基因表達,并有持續(xù)的動作電位,表明他們成功地誘導(dǎo)出心肌細胞。另有學者將MSCs直接注入自體心肌組織內(nèi),發(fā)現(xiàn)有心肌樣細胞形成,具有肌鈣蛋白T和肌球蛋白重鏈染色陽性的心肌細胞特異性標志,表明MSCs在體內(nèi)微環(huán)境條件下可以誘導(dǎo)分化為心肌細胞 近年來,有研究證明中藥能有效地誘導(dǎo)MSCs分化為神經(jīng)元細胞和成骨細胞,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胞在內(nèi)的多種功能細胞,而應(yīng)用中藥成功誘導(dǎo)MSCs分化為神經(jīng)元樣細胞和成骨細胞的研究結(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分化為心肌細胞。 目前國內(nèi)外對中藥能否誘導(dǎo)MSCs分化為心肌細胞的研究還報道甚少,所以我們在眾多的中藥中,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.
【學位授予單位】：廣州中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R329

【參考文獻】

相關(guān)期刊論文 前10條

1 趙越;寧心方合參麥針治療冠心病心絞痛30例臨床觀察[J];浙江中醫(yī)學院學報;2001年04期

2 雷春利，呂文偉，陳羽, 金輝;黃芪總皂甙對在體犬心功能的影響[J];白求恩醫(yī)科大學學報;1994年04期

3 鐘國贛，孫曉霞，李云義, 江巖, 魏永弟，安占元;黃芪皂甙對離體工作心臟的強心作用[J];白求恩醫(yī)科大學學報;1994年05期

4 衛(wèi)永第,劉萬山,高松,權(quán)文富,孫金京,侯令池;人參皂甙Re對細胞膜流動性的雙向調(diào)節(jié)作用[J];白求恩醫(yī)科大學學報;1997年02期

5 唐旭東,姜建青,賃常文,劉寶玉,姜大春,顧大勇;三七總皂甙對心肌缺血-再灌注中中性粒細胞浸潤的影響及其核轉(zhuǎn)錄機制的實驗研究[J];成都中醫(yī)藥大學學報;2002年03期

6 孫曉霞,夏映紅,鐘國贛;人參皂甙單體Rb_1對大鼠在體心臟收縮性能的影響[J];長春中醫(yī)學院學報;2003年01期

7 欒波,梅舉,張寶仁,黃盛東,李志剛;心肌細胞體外微環(huán)境中骨髓間質(zhì)干細胞向心肌樣細胞的分化[J];第二軍醫(yī)大學學報;2003年03期

8 王勁,羅成基,郭朝華,冉新澤,徐輝,粟永萍,程天民;p38及PI3K的激活在IGF-1促進MSCs成肌分化中的作用[J];第三軍醫(yī)大學學報;2003年13期

9 高峰,蔡振杰,俞世強,胡軍,胡巧俠,程亮;大鼠骨髓間充質(zhì)干細胞向心肌細胞的體外誘導(dǎo)分化[J];第四軍醫(yī)大學學報;2002年20期

10 吳鐵軍,蔡振杰,俞世強,胡軍,胡巧霞,趙科研,周和平;不同濃度5-氮胞苷對骨髓間質(zhì)干細胞體外誘導(dǎo)分化的作用[J];第四軍醫(yī)大學學報;2003年15期

相關(guān)會議論文 前1條

1 崔新明;崔亞男;李艷茹;崔麗;;人參皂苷Rg_2對急性心源性休克犬心肌細胞線粒體的保護作用[A];第十三屆全國電子顯微學會議論文集[C];2004年

，

本文編號：2374838