【作者】 郝加虎；

【导师】 叶冬青； 张学军；

【作者基本信息】 安徽医科大学 ， 皮肤病与性病学， 2006， 博士

【摘要】 研究背景 系统性红斑狼疮(systemic lupus erythematosus，SLE)是一种常见典型的自身免疫性疾病，其免疫学特征为患者体内的多克隆自身反应性T、B淋巴细胞激活，产生抗核小体抗体家族(抗核小体抗体、抗组蛋白抗体、抗dsDNA抗体)等大量自身抗体。该病可造成全身多系统、多脏器损害，尤以肾脏损害最严重。SLE病因至今尚未完全明确，可能涉及遗传背景、环境暴露、感染、药物、激素紊乱和免疫异常等因素，其中细胞凋亡异常已成为SLE免疫学发病机制研究热点之一。 细胞凋亡(apoptosis)，又称程序性细胞死亡(programmed cell death，PCD)，1972年由病理学家Kerr LFR等首先提出，是机体在生长、发育及维持内环境稳定过程中由基因控制的自主有序的生理性细胞死亡行为。细胞凋亡通过清除自身反应性淋巴细胞参与自身耐受的形成，维持机体免疫耐受和免疫平衡，而SLE又正是该种免疫耐受与免疫平衡破坏后的结果。 动物模型研究发现，细胞凋亡相关基因的缺陷如fas和fasL基因的缺陷，可直接引起鼠狼疮样综合征；人群研究也显示SLE患者外周血淋巴细胞、单核细胞、更多还原

【Abstract】 Background Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an array of autoantibodies directed against the native nucleosome (nucleosome-specific antibodies), its DNA component (bona fide anti-dsDNA antibodies), and its histone component (bona fide antihistone-specific antibodies) which together compose the large family of antinucleosome antibodies. SLE is associated with a diverse array of clinical manifestations and may affect different organ systems, including lupus nephritis, which is one of the most serious complications in SLE. The etiology of SLE is still unknown so far, and its etiopathogenesis is multifactorial. Multiple genetic and environmental factors, including viruses and other infectious agents, drugs, hormonal factors, and immunological abnormality may contribute to the disease. Insight into the pathogenesis of SLE, however, has deepened in recent years. In particular studies on apoptosis and clearance of apoptotic cells in lupus have shed a new and intriguing light on the development and course of the disease.Apoptosis as early as described by Kerr JFR et al in 1972, also known as programmed cell death (PCD), an essential developmental and homeostatic mechanism, is the preferred physiologic death process for cells and an important immune-response更多还原