本文選題：血管內(nèi)皮細(xì)胞 + 磷脂酰膽堿特異性磷脂酶C(PC-PLC)��； 參考：《山東大學(xué)》2005年博士論文

【摘要】：研究背景和研究目的 血管內(nèi)皮細(xì)胞(Vascular Endothelial Cells,VEC)在血管生成和血管萎縮中起關(guān)鍵作用[Pan X,et al,2004]。血管生成是許多正常生理過程所必需的,如胚胎發(fā)育和傷口愈合[Romagnani P,et al,2004];但血管生成在腫瘤和各種炎癥發(fā)展中也起了十分重要的作用[Griffioen AW,et al,2004]。而血管的萎縮可導(dǎo)致多種心血管疾病(如動脈粥樣硬化、高血壓及血管炎、血管性老年癡呆等)的發(fā)生,目前臨床上此類疾病呈上升趨勢,嚴(yán)重危害著人類的健康。血管萎縮和血管內(nèi)皮細(xì)胞的凋亡有直接相關(guān)性,抑制血管內(nèi)皮細(xì)胞凋亡對阻止血管萎縮具有積極意義。另一方面,誘導(dǎo)腫瘤血管的退化已成為腫瘤治療的一種新方法,誘導(dǎo)腫瘤血管內(nèi)皮細(xì)胞凋亡是誘導(dǎo)腫瘤血管的退化的關(guān)鍵步驟[Greenberger S,et al,2004]。因此研究血管內(nèi)皮細(xì)胞的凋亡機制,可為心血管疾病和腫瘤治療提供理論依據(jù)。 細(xì)胞凋亡是一種復(fù)雜的生理現(xiàn)象,其調(diào)控機制至今不明。血管內(nèi)皮細(xì)胞曾被認(rèn)為是抗凋亡的,因為它能夠抵抗諸如Fas等凋亡誘導(dǎo)劑,除了剝奪基本的存活因子(如生長因子、血清等)外,其他方法很難使其凋亡,因此其凋亡機理的研究也滯后于其他多種細(xì)胞[Sata and Walsh 1998b]。出血性蛇毒是血管內(nèi)皮細(xì)胞有效而專一的凋亡誘導(dǎo)劑,自90年代起就被作為研究血管內(nèi)皮細(xì)胞凋亡機理的工具[Araki S,et al,1993],本論文以出血性蛇毒為工具誘導(dǎo)VEC凋亡,研究其凋亡過程中信號轉(zhuǎn)導(dǎo)途徑。 VEC是錨定依賴性細(xì)胞,只有粘附于細(xì)胞外基質(zhì)上(ECM)才能存活[Feng C,et al,2004]。VEC表面表達(dá)多種ECM成分受體,即膜整聯(lián)蛋白,該種蛋白是存在于質(zhì)膜上跨膜異二聚體糖蛋白,它們不僅使細(xì)胞能正常粘附于基質(zhì)上,還調(diào)節(jié)細(xì)胞的增殖、分化、凋亡等。大量研究表明:細(xì)胞表面所表達(dá)的全部整連蛋白的種類受細(xì)胞分化程度、惡性轉(zhuǎn)化程度等的制約,與細(xì)胞的發(fā)育進(jìn)程密切相關(guān)
[Abstract]:Research background and purpose Vascular Endothelial cells play a key role in angiogenesis and atrophy. Angiogenesis is necessary for many normal physiological processes, such as embryonic development and wound healing [Romagnani Pet alanine], but angiogenesis also plays an important role in the development of tumor and various inflammation. The atrophy of blood vessels can lead to the occurrence of many cardiovascular diseases (such as atherosclerosis, hypertension and vasculitis, vascular dementia and so on). There is a direct correlation between vascular atrophy and vascular endothelial cell apoptosis, and inhibition of vascular endothelial cell apoptosis has positive significance to prevent vascular atrophy. On the other hand, inducing tumor vascular degeneration has become a new method of tumor therapy. Inducing apoptosis of tumor vascular endothelial cells is a key step to induce tumor vascular degeneration. Therefore, studying the mechanism of vascular endothelial cell apoptosis can provide theoretical basis for cardiovascular disease and tumor therapy. Apoptosis is a complex physiological phenomenon and its regulatory mechanism is still unknown. Vascular endothelial cells were once thought to be anti-apoptotic because they were able to resist apoptosis inducers such as Fas, which, apart from depriving basic survival factors (such as growth factors, serum, etc.), are difficult to induce apoptosis. Therefore, the mechanism of apoptosis lags behind that of other cells [Sata and Walsh 1998b]. Hemorrhagic snake venom is an effective and specific apoptosis inducer for vascular endothelial cells. It has been used as a tool to study the mechanism of apoptosis of vascular endothelial cells since 1990s [Araki set alanine 1993]. In this paper, hemorrhagic snake venom was used as a tool to induce apoptosis of VEC. To study the signal transduction pathway in the process of apoptosis. VEC is an anchor-dependent cell. It can survive only by sticking to the extracellular matrix (ECM). VECs express many kinds of ECM component receptors, that is, membrane integrin, which is a transmembrane heterodimeric glycoprotein on the plasma membrane. They not only make cells adhere to matrix normally, but also regulate cell proliferation, differentiation, apoptosis and so on. A large number of studies have shown that the types of all integrin expressed on the cell surface are restricted by the degree of cell differentiation and the degree of malignant transformation, and are closely related to the development of the cell.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R329

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 趙麗,曹英林,孫汶生;鮭魚降鈣素對人乳腺癌細(xì)胞生長作用的實驗研究[J];中國現(xiàn)代普通外科進(jìn)展;2003年01期

2 ;Involvement of gene expressions in apoptosis of vascularendothelial cells induced by rattlesnake venom[J];Cell Research;1999年03期

3 ;Effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenoviruses on antiangiogenesis[J];World Journal of Gastroenterology;2004年10期

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本文編號：1851898