本文選題：微泡造影劑 + 人臍靜脈內(nèi)皮細(xì)胞　； 參考：《中國醫(yī)科大學(xué)》2006年博士論文

【摘要】：前言 隨著分子生物學(xué)的發(fā)展和基因工程技術(shù)的改進(jìn),基因治療的研究不斷取得進(jìn)步。超聲微泡造影劑(USMBCA)的應(yīng)用使得超聲醫(yī)學(xué)不但在診斷方面有所創(chuàng)新,而且其在基因治療方面潛在的應(yīng)用價(jià)值倍受關(guān)注,具有廣闊的應(yīng)用前景。 基因治療時(shí)治療基因必須到達(dá)靶細(xì)胞,進(jìn)入細(xì)胞核,然后再經(jīng)過轉(zhuǎn)錄、翻譯為蛋白質(zhì),才能起到治療作用。基因?qū)塍w內(nèi)的方法有直接注射和靜脈注射法。如果不用某些方式使這些治療性基因保持穩(wěn)定,經(jīng)靜脈注射后通常會(huì)被血清酶快速清除,或很難通過內(nèi)皮細(xì)胞屏障。在靜脈給藥途徑中,要防止基因物質(zhì)在血液中被降解。人們已經(jīng)嘗試用各種不同的被覆物質(zhì)作為基因的載體來改善基因物質(zhì)的轉(zhuǎn)移,新近研究發(fā)現(xiàn),USMBCA可成為基因治療的一種安全、有效的載體。但是,如果使用超聲劑量過大,或微泡造影劑(MBCA)濃度過高時(shí),利用超聲介導(dǎo)MBCA實(shí)現(xiàn)基因的定向轉(zhuǎn)移這一技術(shù)同樣也會(huì)對機(jī)體產(chǎn)生一定的有害的生物學(xué)效應(yīng)。影響USMBCA介導(dǎo)基因治療效果的因素很多,除不同組織和基因種類的影響外,超聲能量、輻照時(shí)間、基因與微泡比例等諸多因素均可對基因治療產(chǎn)生影響。基礎(chǔ)研究的意義是為了臨床應(yīng)用,雖然在基因治療中超聲介導(dǎo)微泡可通過空化效應(yīng)增加內(nèi)皮細(xì)胞間隙和細(xì)胞膜的通透性,從而使治療基因進(jìn)入靶細(xì)胞;但同時(shí)也可能引起一定的組織損傷。因此,為了該項(xiàng)技術(shù)在臨床中安全有效地應(yīng)用,對超聲介導(dǎo)MBCA各種相關(guān)的參數(shù)進(jìn)行深入的研究是十分必要的。 本研究旨在:通過觀察超聲介導(dǎo)MBCA對體外培養(yǎng)的人臍靜脈內(nèi)皮細(xì)胞(HUVEC)的作用,靜脈注射USMBCA對大鼠心肌組織毛細(xì)血管及肌纖維的作用,以及使用超聲介導(dǎo)MBCA對綠色熒光蛋白報(bào)告基因(EPGFP)對HUVEC的轉(zhuǎn)染效率的影響,探討USMBCA是否可以作為基因治療的一種
[Abstract]:PrefaceWith the development of molecular biology and the improvement of genetic engineering technology, the research of gene therapy has made progress.The application of ultrasound microbubble contrast agent USMBCAmakes ultrasound medicine not only be innovated in diagnosis, but also its potential application value in gene therapy has attracted much attention and has a broad application prospect.In gene therapy, the therapeutic gene must reach the target cell, enter the nucleus, and then be transcribed and translated into protein to play a therapeutic role.Direct injection and intravenous injection are the methods of gene transfer in vivo.If these therapeutic genes are not stabilized in some way, they are usually quickly cleared by serum enzymes after intravenous injection, or are difficult to pass through the endothelial cell barrier.During intravenous administration, genetic substances are prevented from degrading in the blood.People have tried to use a variety of coated materials as gene carriers to improve gene transfer. Recently, USMBCA has been found to be a safe and effective vector for gene therapy.However, if the dose of ultrasound is too high or the concentration of microbubble contrast agent is too high, the technology of directed gene transfer by ultrasound mediated MBCA will also produce some harmful biological effects on the body.There are many factors that affect the effect of gene therapy mediated by USMBCA. In addition to different tissues and gene types, ultrasound energy, irradiation time, gene / microbubble ratio and many other factors can affect gene therapy.The significance of basic research is for clinical application, although ultrasound mediated microbubbles can increase the permeability of endothelial cell space and cell membrane through cavitation effect in gene therapy, so that therapeutic gene can enter target cells.But at the same time, it may cause some tissue damage.Therefore, in order to safely and effectively apply this technique in clinic, it is necessary to study various parameters related to ultrasound mediated MBCA.The purpose of this study was to observe the effects of ultrasound mediated MBCA on cultured human umbilical vein endothelial cells (HUVECs) and the effects of intravenous USMBCA on the capillaries and muscle fibers in rat myocardium.The effect of ultrasound mediated MBCA on the transfection efficiency of green fluorescent protein reporter gene (EGFP) on HUVEC was also discussed. Whether USMBCA could be used as a gene therapy was discussed.
【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R346

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本文編號：1750005