本文選題：ICAM-1 + 單鏈抗體　； 參考：《吉林大學(xué)》2008年博士論文

【摘要】： 炎癥是機(jī)體的一種重要的基本病理過(guò)程。各種炎癥雖然有其特殊性,但從局部的病理變化看來(lái),它們有著不少共同點(diǎn),即都是機(jī)體對(duì)致炎因子的損傷作用所產(chǎn)生的一種反應(yīng),最新的醫(yī)學(xué)研究發(fā)現(xiàn),當(dāng)炎癥的程度嚴(yán)重或發(fā)展成慢性炎癥時(shí),它可能導(dǎo)致腫瘤、心血管疾病、糖尿病、自身免疫性疾病以及與年齡相關(guān)的疾病(如關(guān)節(jié)炎、早老性癡呆病、骨質(zhì)疏松癥等)的發(fā)生。細(xì)胞間粘附分子-1(ICAM-1)作為重要的致炎因子,在炎癥反應(yīng)、免疫監(jiān)督等過(guò)程中起著重要的作用。以上許多疾病過(guò)程中可見(jiàn)ICAM-1的異常表達(dá),因此阻遏ICAM-1的表達(dá)為以上疾病的診斷和治療提供了新的策略。 本研究在已制備的抗ICAM-1單克隆抗體的基礎(chǔ)上,從分泌該單抗的雜交瘤細(xì)胞株中克隆出VH和VL基因,組裝成ScFv基因,將ScFv基因插入原核表達(dá)載體pET-22b(+)中,轉(zhuǎn)化宿主菌中進(jìn)行表達(dá),之后對(duì)表達(dá)的包涵體進(jìn)行了復(fù)性和純化。最后通過(guò)體外細(xì)胞實(shí)驗(yàn)和體內(nèi)動(dòng)物實(shí)驗(yàn)檢測(cè)ScFv抗體的生物學(xué)活性。細(xì)胞實(shí)驗(yàn)表明,制備的ScFv能有效地抑制內(nèi)皮細(xì)胞與單核細(xì)胞之間的粘附;動(dòng)物實(shí)驗(yàn)證明此ScFv對(duì)小鼠無(wú)菌性炎癥有明顯的抑制作用。本課題為進(jìn)一步治療炎癥性疾病奠定了基礎(chǔ)。
[Abstract]:Inflammation is an important basic pathological process of the body. Although various kinds of inflammation have their own particularity, but from the local pathological changes, they have a lot in common, that is, they are all a kind of reaction of the body to the injury of inflammatory factor, the latest medical research found, When inflammation is severe or develops into chronic inflammation, it can lead to tumours, cardiovascular diseases, diabetes, autoimmune diseases, and age-related diseases such as arthritis, Alzheimer's disease, osteoporosis, etc. Intercellular adhesion molecule-1 (ICAM-1), as an important inflammatory factor, plays an important role in inflammatory response and immune supervision. The abnormal expression of ICAM-1 can be seen in many of the above diseases, so the repressive expression of ICAM-1 provides a new strategy for the diagnosis and treatment of these diseases. In this study, VH and VL genes were cloned from hybridoma cell lines secreting the monoclonal antibodies against ICAM-1, and ScFv gene was assembled into the prokaryotic expression vector pET-22b (). The VH and VL genes were expressed in the transformed host strain. After that, the expressed inclusion bodies were renatured and purified. Finally, the biological activity of ScFv antibody was detected by in vitro cell experiment and in vivo animal experiment. Cell experiments showed that the prepared ScFv could effectively inhibit the adhesion between endothelial cells and monocytes, and that the ScFv could inhibit the aseptic inflammation in mice. This topic has laid the foundation for the further treatment of inflammatory diseases.
【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】：2008
【分類號(hào)】：R392.12

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