【作者】 赵海全；

【导师】 郑文岭； 马文丽；

【作者基本信息】 第一军医大学 ， 生物化学与分子生物学， 2006， 博士

【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，更多还原

【Abstract】 Background and Objective Herpes simplex virus (HSV) is the viral agent of genital herpes (GH) in mankind worldwide. Researchs in epidemiology showed seropositive for HSV were increasing obviously in most countries in the past 20 years. GH recurrents easily, which harm the patients heavily. GH expends lots of publical health resource as well as aggravates economic burden. GH in pregnant women may cause deadly infection in newborn children and foetuses. GH also increases the fatalness of HIV-infection in AIDS era. Effective therapy and vaccines are not available at present. Following primary infection, neutralizing antibodies to HSV develop in the serum. Subsequently, some seropositive individuals develop clinically mild recurrent labial or genital lesions, typifying the unique biological property of HSV, namely an ability to recur in the presence of humoral immunity or reactivation of latent infection. The spectrum of disease caused by HSV includes primary and recurrent infections of mucous membranes (e.g., gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections in immunocompromised hosts, HSV encephalitis, Kaposi’s varicella-like eruption, and an association with erythema multiforme, and related with cervix carcinoma and Atherosclerosis (AS). An important advance in our knowledge of HSV infections has been the ability to distinguish between HSV-1 and HSV-2. HSV-1 is more frequently associated with nongenital infection, while HSV-2 is associated with genital disease. HSV has two unique biological properties that influence human disease. Although HSV-1 and HSV-2 are usually transmitted by different routes and involve different areas of the body, there is an overlap in the epidemiology and clinical manifestations. Virus is transmitted from infected to susceptible individuals during close personal contact. There is no seasonal variation in the incidence of infection. Because HSV infection is rarely fatal, and HSV更多还原