磷酯酰胆碱特异性磷脂酶C和膜整联蛋白β4调节血管内皮细胞凋亡信号通路的研究

发布时间：2018-05-06 10:11

本文选题：血管内皮细胞 + 磷脂酰胆碱特异性磷脂酶C(PC-PLC)　；参考：《山东大学》2005年博士论文

【摘要】：研究背景和研究目的血管内皮细胞(Vascular Endothelial Cells,VEC)在血管生成和血管萎缩中起关键作用[Pan X,et al,2004]。血管生成是许多正常生理过程所必需的,如胚胎发育和伤口愈合[Romagnani P,et al,2004];但血管生成在肿瘤和各种炎症发展中也起了十分重要的作用[Griffioen AW,et al,2004]。而血管的萎缩可导致多种心血管疾病(如动脉粥样硬化、高血压及血管炎、血管性老年痴呆等)的发生,目前临床上此类疾病呈上升趋势,严重危害着人类的健康。血管萎缩和血管内皮细胞的凋亡有直接相关性,抑制血管内皮细胞凋亡对阻止血管萎缩具有积极意义。另一方面,诱导肿瘤血管的退化已成为肿瘤治疗的一种新方法,诱导肿瘤血管内皮细胞凋亡是诱导肿瘤血管的退化的关键步骤[Greenberger S,et al,2004]。因此研究血管内皮细胞的凋亡机制,可为心血管疾病和肿瘤治疗提供理论依据。细胞凋亡是一种复杂的生理现象,其调控机制至今不明。血管内皮细胞曾被认为是抗凋亡的,因为它能够抵抗诸如Fas等凋亡诱导剂,除了剥夺基本的存活因子(如生长因子、血清等)外,其他方法很难使其凋亡,因此其凋亡机理的研究也滞后于其他多种细胞[Sata and Walsh 1998b]。出血性蛇毒是血管内皮细胞有效而专一的凋亡诱导剂,自90年代起就被作为研究血管内皮细胞凋亡机理的工具[Araki S,et al,1993],本论文以出血性蛇毒为工具诱导VEC凋亡,研究其凋亡过程中信号转导途径。 VEC是锚定依赖性细胞,只有粘附于细胞外基质上(ECM)才能存活[Feng C,et al,2004]。VEC表面表达多种ECM成分受体,即膜整联蛋白,该种蛋白是存在于质膜上跨膜异二聚体糖蛋白,它们不仅使细胞能正常粘附于基质上,还调节细胞的增殖、分化、凋亡等。大量研究表明:细胞表面所表达的全部整连蛋白的种类受细胞分化程度、恶性转化程度等的制约,与细胞的发育进程密切相关
[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.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R329

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