本文選題：干細(xì)胞 + 分化　； 參考：《吉林大學(xué)》2012年碩士論文

【摘要】：冠心病(coronary heart disease,CHD)是心血管疾病的的一個(gè)主要病種，在我國每年導(dǎo)致超過一百萬患者死亡。冠狀動(dòng)脈狹窄引起心肌缺血，導(dǎo)致心肌細(xì)胞的供氧和供能不足，心肌細(xì)胞代謝受阻，不能夠支持心臟的正常工作，并引起心絞痛。長期的供氧供能不足導(dǎo)致心肌細(xì)胞（Cardiomyocytes,CMs）受損，死亡，數(shù)量減少，引起疤痕組織形成，導(dǎo)致心室重構(gòu)，從而進(jìn)一步引起心臟功能受損甚至危害生命。 傳統(tǒng)觀念認(rèn)為心肌細(xì)胞是不可再生細(xì)胞，一旦發(fā)生損害就無法修復(fù)，心肌損傷后的心肌細(xì)胞如何補(bǔ)充修復(fù)是困擾醫(yī)學(xué)界的一個(gè)難題。在目前的治療方案中，，藥物治療確實(shí)能夠延緩心肌細(xì)胞的損傷和死亡，減慢心臟的衰竭，但是藥物并不能夠從根本上解決問題。目前唯一有效的可行的治療心臟衰竭的途徑是心臟移植，然而，供體心臟的不足和移植后免疫排斥反應(yīng)嚴(yán)重的限制了心臟移植對(duì)解決廣大患者的應(yīng)用。心肌細(xì)胞再生可以提供一個(gè)當(dāng)前可行的解決方案，是目前科學(xué)家和臨床醫(yī)生們解決包含冠心病等多種心血管疾病的希望與挑戰(zhàn)。 近些年來，隨著細(xì)胞治療技術(shù)研究的深入，利用細(xì)胞移植的方法來替代補(bǔ)充機(jī)體損傷或死亡的細(xì)胞來修復(fù)受損組織的方法，已經(jīng)成為當(dāng)今醫(yī)學(xué)研究領(lǐng)域中的一個(gè)重點(diǎn)研究方向。大量研究表明，人骨髓間充質(zhì)干細(xì)胞(human bone marrow mesenchymal stem cells，hBMSCs)具有高度增殖、自我更新能力及多分化潛能,在不同的誘導(dǎo)條件下可分化為各種不同類型的組織細(xì)胞。BMSCs可以分化為心肌細(xì)胞(cardiomyocytes cell，CMs)，但其機(jī)制尚不明了。 目前體外骨髓間充質(zhì)干細(xì)胞向心肌細(xì)胞誘導(dǎo)分化研究主要限于通過5-Aza（5-氮雜胞苷）對(duì)其進(jìn)行成心肌細(xì)胞誘導(dǎo)。雖然通過5-Aza的誘導(dǎo)，hBMSCs可以誘導(dǎo)分化為心肌細(xì)胞，但間充質(zhì)干細(xì)胞的可塑性依賴于其所處的微環(huán)境，然而體外誘導(dǎo)實(shí)驗(yàn)并沒有完全模擬冠狀動(dòng)脈狹窄后心肌細(xì)胞處于缺血缺氧的微環(huán)境，這種微環(huán)境的變化引起心肌細(xì)胞氧化應(yīng)激損傷。氧化應(yīng)激時(shí)，細(xì)胞活性氧的產(chǎn)生與清除之間的平衡被打破，機(jī)體內(nèi)堆積大量的超氧陰離子、羥自由基和過氧化氫(H_2O_2)等自由基，這些氧自由基能夠?qū)θ梭w的正常功能產(chǎn)生很大的危害。近些年來隨著研究的逐步深入，世界各地的生物醫(yī)學(xué)領(lǐng)域的科研工作者對(duì)與冠心病相關(guān)的心肌細(xì)胞缺血、心肌細(xì)胞氧化應(yīng)激損傷等復(fù)雜的病理生理變化進(jìn)行了更為深入的科學(xué)研究。 本實(shí)驗(yàn)以體外培養(yǎng)人來源骨髓間充質(zhì)干細(xì)胞（hBMSCs）為對(duì)象，探討5-Aza誘導(dǎo)hBMSCs向心肌細(xì)胞分化的機(jī)制及氧化應(yīng)激損傷的hBMSCs分化為心肌細(xì)胞的可能性。 H2O2可以模擬局部缺氧、氧化應(yīng)激的微環(huán)境，在這種微環(huán)境下研究5-Aza還能否繼續(xù)誘導(dǎo)hBMSCs向心肌細(xì)胞分化。本實(shí)驗(yàn)將為hBMSCs修復(fù)替代受損心肌等的細(xì)胞移植提供實(shí)驗(yàn)依據(jù)及理論基礎(chǔ),從而為冠心病等心血管疾病的治療開辟新的方法。
[Abstract]:Coronary heart disease (heart) is one of the major cardiovascular diseases, which causes more than 1 million deaths in China every year. Coronary artery stenosis causes myocardial ischemia, which leads to insufficient oxygen supply and energy supply, blocked metabolism of myocardial cells, and can not support the normal operation of the heart and cause angina pectoris. Long-term lack of oxygen supply leads to the damage of cardiomyocytes-CMs, death, decrease in the number, scar tissue formation, ventricular remodeling, and further damage to heart function and even endanger life. The traditional view is that myocardial cells are non-renewable cells, once damage can not be repaired, how to repair myocardial cells after myocardial injury is a difficult problem in medical field. In the current treatment, drug therapy can delay myocardial cell injury and death, slow down heart failure, but drugs can not solve the problem fundamentally. At present, the only effective and feasible way to treat heart failure is heart transplantation. However, the shortage of donor heart and the post-transplant immune rejection seriously limit the application of heart transplantation to solve patients. Cardiomyocyte regeneration can provide a feasible solution for scientists and clinicians to solve the challenges of cardiovascular diseases including coronary heart disease. In recent years, with the development of cell therapy technology, it has become an important research direction in the field of medical research to replace the method of cell transplantation to repair damaged tissue by replacing the damaged or dead cells. A large number of studies have shown that human bone marrow mesenchymal stem cells hBMSCs have high proliferation, self-renewal and multi-differentiation potential. Under different induction conditions, BMSCs could differentiate into different types of tissue cells. BMSCs could differentiate into cardiomyocytes, but its mechanism was not clear. At present, the study on the differentiation of bone marrow mesenchymal stem cells into cardiomyocytes in vitro is mainly limited to the induction of cardiac myocytes by 5-Azaan5-azacytidine (5-Aza-5-azacytidine). Although hBMSCs can be induced to differentiate into cardiomyocytes by 5-Aza, the plasticity of mesenchymal stem cells depends on their microenvironment. However, in vitro induction experiments did not completely mimic the ischemic and hypoxic microenvironment of myocardial cells after coronary artery stenosis, which resulted in oxidative stress injury of cardiomyocytes. During oxidative stress, the balance between the production and elimination of reactive oxygen species was broken, and a large number of superoxide anions, hydroxyl radicals and H _ S _ 2O _ 2 were accumulated in the body. These oxygen free radicals can do great harm to the normal function of human body. In recent years, with the gradual deepening of research, researchers in the biomedical field around the world have done research on myocardial ischemia related to coronary heart disease. The complex pathophysiological changes of myocardial cells such as oxidative stress injury have been studied more deeply. Human bone marrow mesenchymal stem cells (hBMSCs) were cultured in vitro to investigate the mechanism of hBMSCs differentiation into cardiomyocytes induced by 5-Aza and the possibility of oxidative stress induced hBMSCs differentiation into cardiomyocytes. H2O2 can simulate the microenvironment of hypoxia and oxidative stress in which 5-Aza can continue to induce the differentiation of hBMSCs into cardiomyocytes. This study will provide experimental basis and theoretical basis for hBMSCs repair and replacement of damaged myocardium cells, thus opening up a new method for the treatment of cardiovascular diseases such as coronary heart disease.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R329

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