本文選題：基因治療 + 成纖維細(xì)胞��； 參考：《吉林大學(xué)》2006年博士論文

【摘要】： 基因治療有可能成為人類最終征服許多難治性疾病的一種新的治療手段。如何將目的基因安全、高效、靶向性地導(dǎo)入人體內(nèi)特定器官、組織,并在靶細(xì)胞內(nèi)表達(dá)是目前有待解決的難題之一。 我們觀察了成纖維細(xì)胞在診斷劑量的超聲波及聯(lián)合應(yīng)用超聲造影劑作用下的電鏡改變,發(fā)現(xiàn)細(xì)胞膜表面形成一些可逆性的小孔。說明診斷劑量的超聲波聯(lián)合超聲造影劑對(duì)細(xì)胞的損害作用是輕微的、可逆的。 我們觀察了診斷劑量范圍不同超聲強(qiáng)度對(duì)體內(nèi)外基因轉(zhuǎn)染的影響,得出如下結(jié)論:MI(mechanism index)為1.4的超聲劑量與超聲造影劑聯(lián)合適合作用于體外培養(yǎng)細(xì)胞;而超聲聯(lián)合造影劑應(yīng)用于體內(nèi)細(xì)胞的基因轉(zhuǎn)染時(shí),MI為1.6的超聲劑量比較合適。 在轉(zhuǎn)染后成纖維細(xì)胞血管內(nèi)皮細(xì)胞生長(zhǎng)因子(Vascular endothelial cell growth factor)VEGF165蛋白表達(dá)的定量研究中,發(fā)現(xiàn)超聲聯(lián)合造影劑不但可促進(jìn)基因的轉(zhuǎn)染,對(duì)基因的表達(dá)也有促進(jìn)作用。 體內(nèi)部分實(shí)驗(yàn),我們?cè)O(shè)計(jì)了大鼠背部隨意皮瓣的動(dòng)物模型,結(jié)果表明,超聲聯(lián)合造影劑能夠促進(jìn)VEGF基因的體內(nèi)轉(zhuǎn)染,使缺血皮瓣毛細(xì)血管生成增多,皮瓣成活面積增加。通過本實(shí)驗(yàn)說明診斷劑量超聲聯(lián)合超聲造影劑是一種安全、有效、簡(jiǎn)便的促進(jìn)基因轉(zhuǎn)染的方法。把超聲聯(lián)合造影劑這種新的轉(zhuǎn)基因方法擴(kuò)展到組織移植方面的研究中來,為創(chuàng)傷修復(fù)提供了一種簡(jiǎn)捷、高效的途徑。
[Abstract]:Gene therapy may become a new method to conquer many refractory diseases. How to transfer the target gene safely, efficiently and targeted into specific organs and tissues and express it in target cells is one of the difficult problems to be solved. We observed the electron microscopic changes of fibroblasts under the action of diagnostic dose of ultrasound and ultrasound contrast medium, and found that some reversible pores were formed on the surface of cell membrane. The results showed that the damage of diagnostic dose of ultrasound combined with ultrasound contrast agent on cells was mild and reversible. We observed the effects of different ultrasound intensities on gene transfection in vitro and in vivo. The conclusions are as follows: the ultrasound dose of 1. 4% MImechanism and ultrasound contrast agent are suitable for cell culture in vitro. However, ultrasound combined with contrast agent was more suitable for gene transfection with an ultrasound dose of 1.6. In the quantitative study on the expression of vascular endothelial cell growth factor)VEGF165 protein of vascular endothelial growth factor (VEGF) in fibroblasts after transfection, it was found that ultrasound combined with contrast agent could not only promote gene transfection, but also promote gene expression. In some experiments in vivo, we designed an animal model of random dorsal flap in rats. The results showed that ultrasound combined with contrast agent could promote the transfection of VEGF gene in vivo, increase capillary formation and increase the survival area of ischemic flap. The results show that the diagnostic dose ultrasound combined with ultrasound contrast agent is a safe, effective and simple method to promote gene transfection. The application of ultrasound combined with contrast agent to the study of tissue transplantation provides a simple and efficient way for wound repair.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R346

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本文編號(hào)：1980158