HSV-2感染ECV304细胞的生物学效应研究

发布时间：2019-05-09 01:50

【摘要】：单纯疱疹病毒(Herpes Simplex Virus，HSV)是世界范围内人类生殖器疱疹(Genital herpes，G H)的病毒病原。流行病学调查研究显示，过去20年中，世界大多数国家HSV的血清患病率显著增加。该病易反复发作，给患者造成巨大的身心痛苦。同时GH还消耗大量公共卫生资源，给个人和社会带来沉重经济负担。孕妇GH尚会影响优生优育，可引起胎儿、新生儿的严重感染，导致严重不良后果。在HIV／AIDS流行地区，GH还增加了感染HIV的危险性。目前尚无安全有效的疫苗和药物能预防、治愈HSV感染。HSV感染引发的疾病包括原发和继发的粘膜感染(如龈口炎、唇疱炎和生殖器疱疹)、角膜炎、新生儿HSV感染、内脏HSV感染、HSV脑炎、水痘样出疹和多形红斑，并与宫颈癌和动脉粥样硬化(AS)的发生有关。动脉粥样硬化(AS)严重威胁人类健康，虽然大量的流行病学资料显示传统的危险因子是动脉粥样硬化的主要危险因素，但动脉粥样硬化仍然有许多潜在的病因亟待探索。研究表明，病原微生物感染可能参与了动脉粥样硬化的发生发展，感染后的炎症反应在动脉粥样硬化的发生过程中发挥重要作用。有关病毒感染与AS的关系逐渐受到人们重视，血清流行病学和分子生物学的研究资料表明，HSV及其DNA序列存在于AS的病灶组织，主要见于血管平滑肌细胞(SMC)和内皮细胞(EC)，且AS患者血清HSV的抗体阳性率明显增高，提示HSV的感染在AS的形成和发生发展过程中可能起重要作用。迄今为止，对于HSV如何参与AS的发病机制尚缺乏深入的了解，病毒对体外靶细胞的作用可以反映病毒对体内细胞的直接作用，研究体外情况下HSV感染血管内皮细胞的生物学效应，对阐明HSV的致病机制具有非常重要的意义。目前研究发现，HSV可通过内皮毒性作用、损害内皮依赖的舒张功能及影响内皮粘附功能等方式造成内皮结构和功能损伤，，但其潜在的基因水平的机制尚不清楚。传统的RNA方法学如Northern斑点杂交分析一次只能研究一种基因，成本高，效率低，
[Abstract]:Herpes simplex virus (Herpes Simplex Virus,HSV) is a worldwide viral pathogen of human genital herpes H (Genital herpes,G H). Epidemiological research shows that in the past 20 years, the seroprevalence of HSV has increased significantly in most countries of the world. The disease is prone to recurrent attacks, causing great physical and mental pain to the patient. At the same time, GH also consumes a lot of public health resources, bringing heavy economic burden to individuals and society. Pregnant women GH will also affect eugenics, can cause severe fetal, neonatal infection, leading to serious adverse consequences. In HIV/AIDS endemic areas, GH also increases the risk of HIV infection. There are no safe and effective vaccines and drugs to prevent and cure HSV infection. The diseases caused by HSV infection include primary and secondary mucosal infections (such as gingivitis, livitis and genital herpes), keratitis and neonatal HSV infection. Visceral HSV infection, HSV meningitis, pimple rash and erythema multiforme are associated with cervical cancer and atherosclerosis (AS). Atherosclerosis (AS) is a serious threat to human health. Although a large number of epidemiological data show that traditional risk factors are the main risk factors of atherosclerosis, there are still many potential causes of atherosclerosis that need to be explored. Studies have shown that pathogenic microbial infection may be involved in the occurrence and development of atherosclerosis, and the inflammatory response after infection plays an important role in the occurrence of atherosclerosis. The relationship between viral infection and AS has been paid more and more attention. Seroepidemiological and molecular biology data show that HSV and its DNA sequence exist in the lesion tissue of AS. The positive rate of serum HSV antibody in patients with vascular smooth muscle cell (SMC) and endothelial cell (EC), was significantly higher than that in patients with AS, suggesting that HSV infection may play an important role in the formation, occurrence and development of AS. Up to now, there is still a lack of in-depth understanding of how HSV participates in the pathogenesis of AS. The effect of virus on target cells in vitro can reflect the direct effect of virus on cells in vivo. To study the biological effects of HSV infection on vascular endothelial cells in vitro is of great significance for elucidating the pathogenesis of HSV. At present, it has been found that HSV can cause endothelial structure and function damage through endotoxicity, damage endothelium-dependent diastolic function and endothelial adhesion function, but the mechanism of its potential gene level is not clear. Traditional RNA methods, such as Northern dot blot hybridization, can only study one gene at a time, with high cost and low efficiency.
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R373

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