最近证据表明细胞坏死也可是程序化的和耗能的，称为程序化坏死。我们的研究表明，坏死细胞可诱导中性粒细胞坏死，为中性粒细胞程序化坏死提供了新的证据。本课题拟研究中性粒细胞程序化坏死的机制和作用：1、探讨中性粒细胞程序化坏死的诱导细胞或诱导分子，重点阐明HMGB-1、TNF-α、LPS等分子对粒细胞程序化坏死的作用；2、分析TLR、TNFR、RIP1/RIP3、Caspase8、ATP、ROS等分子在程序化坏死的信号传导以及细胞膜破坏等过程中所起的作用；3、比较中性粒细胞程序化坏死与非程序化坏死过程中的异同，重点研究其细胞形态的变化，以及释放信号分子的差异；4、在RA模型中，观察中性粒细胞程序化坏死的作用及机制，以及阻断相应信号通路对RA的治疗作用。本研究对揭示中性粒细胞程序化坏死的机制，及其在炎症、感染以及RA发病中的作用有非常重要的意义，并为抗炎和抗感染治疗提供新的思路和方法。

Necrosis has recently been demonstrated to be programmatic and energy comsuming, a process termed necroptosis. Our recent study has shown that neutrophil necrosis could be induced by necrotic cells, which provides a new evidence for neutrophil necroptosis. In this project, we aim to investigate the mechanisms and the effects of neutrophil necroptosis: 1. to investigate the cells and the molecular mechanisms that induce neutrophil necroptosis, mainly focusing on the roles of HMGB-1,TNF-α and LPS, 2. to illustrate the effects of some molecules such as TLR, TNFR, RIP1/RIP3, Caspase8, ATP and ROS in the process of sigal transduction and membrane damage during necroptosis, 3. to identify the similarities and differences between traditional necrosis and necroptosis in the aspects of morphologigical changes and inflammatory cytokine release, 4. to find out the effects and mechanisms of neutrophil necroptosis in a rheumatoid arthritis mouse model and the therapeutic effect of blocking one or several pathways in the pathogenesis of rheumatoid arthritis.This study will not only unravel the mechanisms of neutrophil necroptosis, elucidate its roles and significances in inflammation, infection and the pathogenesis of RA, but also shed new light on anti-inflammatory and anti-infection therapy.