中性粒细胞源性的凋亡微粒参与SLE发病及其机制的研究

Systemic lupus erythematosus (SLE) is an autoimmune disease which involves multi-system and heavily threatens the health of human body. Evidence showed the apoptosis of neutrophils increased in SLE patients, which corresponded to the activity of disease, compared with normal healthy people; however, the role of microparticles produced by neutrophils during early apoptosis in the pathogenesis of SLE remained unclear and there is no related report so far. The pre-research of applicant aboard found that neutrophil-derived apoptotic microparticles inhibited the activity and proliferation of naive CD4+ T cells. Neutrophil-derived apoptotic microparticles of SLE patients may display difference to those of normal healthy people, which might cause the disorder of CD4+ T function and take part in the pathogenesis of SLE. This project will at first study on the quantity difference and phenotypic variety of neutrophil-derived microparticles in the peripheral blood of SLE compared to normal healthy donor; then evaluate the alteration of effect by neutrophil-derived apoptotic microparticles of SLE patients on naive CD4+ T cell activity and function, compared to normal healthy donor; at last, in this project the neutrophil-derived apoptotic microparticles will be injected subcutaneously into mice, trying to establish a SLE model . This research will investigate the importance of neutrophil-derived apoptotic microparticles in the pathogenesis of SLE based on the SLE patients and animal experiments in vitro and in vivo, and this might provide new scientific evidence to reveal the pathogenesis of SLE.

SLE是严重危害人类身体健康的多系统损害的自身免疫性疾病。研究发现中性粒细胞（PMNs）的凋亡在SLE较正常人增加，同时与疾病的活动度相关；但PMNs凋亡早期形成的凋亡微粒在SLE中作用不明，目前也无相关报道。申请人留学期间研究发现正常人PMNs源性凋亡微粒对幼稚CD4+ T细胞的活化增殖起抑制作用。PMNs的凋亡微粒来源于SLE患者可能与正常人不同使CD4+ T细胞功能紊乱，参与SLE的发病。故本项目先探讨SLE患者外周血中的PMNs源性凋亡微粒较正常人是否在数量和表型上有差异；再探讨其对幼稚CD4+ T的活化增殖的影响与正常人比较是否具有差别；最后通过对小鼠注射PMNs体外诱导产生的凋亡微粒后看能否诱导出SLE。本项目从病人、动物两方面的体内外实验探讨PMNs源性凋亡微粒在SLE发病中的作用，为进一步揭示SLE发病机制提供科学依据。

系统性红斑狼疮（SLE）是严重危害人类身体健康的多系统损害的自身免疫性疾病，其发病机制不明。目前对于SLE患者的循环细胞微粒的研究结果存在矛盾。本研究通关过流式细胞术对52例SLE患者和34例健康对照者的外周血中的微粒进行了检测，发现总微粒数和中性粒细胞来源的微粒数在SLE患者外周循环中增加，而凋亡微粒和内皮细胞来源/血小板来源的微粒数并无明显差异。通过ELISA方法检测了SLE患者和健康对照者血浆中的FGF basic/FGF 23和pentraxn 3的表达水平，发现FGF23和pentraxin 3在SLE患者血浆中表达增高，同时FGF23 与SLE患者24小时尿蛋白定量成正相关，而pentraxin 3与SLEDAI评分和ESR成正相关，与C3补体水平成负相关。以上结果提示循环总微粒和中性粒细胞来源微粒可能参与SLE疾病，而FGF23可能成为评估狼疮肾炎严重程度的新指标，pentraxin 3作为SLE疾病活动度的补充评价因素对于指导临床决策具有重要意义。