自身凋亡DNA诱导的SLE疾病动物模型的建立及其特性研究

系统性红斑狼疮（SLE）是一种病因复杂、多器官受累、致死性严重自身免疫病和自身免疫病研究原型，其发病不断攀升而机制不明。现有的多种SLE动物模型虽一定程度模拟了SLE发病过程，但基于特殊遗传背景的自发性SLE模型和由化学物质及异体抗原诱导的SLE模型机制纷繁，差异巨大，难以用于常规遗传背景人群SLE发病机制、防治策略研究及相关的药物筛选。本研究拟以多年研究为基础，建立和完善一种基于常规遗传背景小鼠、以明确的自身低甲基化凋亡DNA（ALD-DNA）诱导的SLE动物模型，建立该模型自身抗体谱、炎症细胞因子谱、病理及细胞学特征全景，观测该模型的稳定性和可控性，深入探讨SLE发病的免疫学机制，并以临床一线治疗方案探讨和验证该模型的稳定性和药效评估价值。旨在弥补现有SLE动物模型不足，发展通用稳定、抗原明确的SLE模型，推动SLE基础和临床研究。

Systemic lupus erythematosus (SLE) is a complex, multiple organs involved, potentially fatal disease and also the prototype of other autoimmune disease. The disease incidence is increased recently throughout the world and especially in China. However, the mechanisms involved in the pathogenesis of SLE disease remain unknown. Although the existing lupus models could partially imitate the disease course of SLE, the numerous and complicated mechanisms involved in the spontaneous lupus mouse models established on the susceptible genetic background and the induced lupus models triggered by the chemic components (for example: pristine) or xenogenic antigens, are hardly used for the pathogenesis mechanism exploration, preventive and therapeutic strategy development and pharmaceutical screening in SLE patients with general genetic background. In the present study, a SLE murine model was established and consummated on the general genetic background through immunizing with a self specific hypomethylated dsDNA. The characteristic spectrum of autoantibodies, proinflammatory cytokines, pathology and cytology, would be set up and the stability and controllability of this SLE murine model would be detected. Moreover, the analysis of cellular and molecular mechanisms involved in the pathogenesis of the SLE murine model would be performed. The classical Rx would be used to treat the lupus mice to explore the stability of this SLE murine model and validity of the classical Rx on the SLE murine model. Taken together, our established lupus murine model could fetch up the insufficiency of the existing lupus models, and the self specific antigen-induced stable SLE murine model which could be universally used, might push the progress of the basic and clinical study on SLE disease.