抗中性粒细胞胞浆抗体（ANCA）诱导中性粒细胞损伤血管内皮是ANCA相关血管炎（AAV）的病因，但既往研究表明中性粒细胞对内皮细胞的损伤依赖活化血小板的存在。AAV患者血中五聚体C反应蛋白（pCRP）明显升高。课题组近期发表的文章证明，ANCA可通过中性粒细胞诱捕网使pCRP解聚为单体（mCRP），mCRP可活化血小板并释放中性粒细胞激活因子HMGB-1，提示mCRP可以血小板为桥梁辅助ANCA诱导中性粒细胞的活化。初步证明这种作用是由mCRP通过aa35-47与血小板脂筏结合而实现的。本研究拟通过基因重组aa35-47突变mCRP研究mCRP与血小板脂筏结合特性及信号通路；利用流体小室、激光共聚焦及活体成像等技术研究mCRP活化的血小板对ANCA诱导中性粒细胞损伤血管内皮的影响；观察mCRP生成抑制剂1,6-bis(PC)-H对AAV模型大鼠的肾保护作用，为探索AAV发病机制提供新思路。

Antineutrophil cytoplasmic antibodies (ANCA) can induce the activation of neutrophils and then injure the endothelial cells. Although this process has been considered as the causative factor of ANCA associated vasculitis (AAV), the adequate activation of neutrophils by ANCA needs the existence of some cofactors. Previous studies indicate that the injury of endothelial cells taken by neutrophils needs the existence of activated platelets. There are high levels of circulating pentameric C reactive protein (pCRP) in patients with active AAV. Our previous work which has been published recently demonstrates that the pCRP can dissociate into the monomeric form (mCRP) in AAV. These newly formed mCRP can bind and activate static platelets. The activated platelets then release high-mobility group protein 1 (HMGB-1), an activator of neutrophils. This indicates that mCRP can enlarge the ANCA-induced activation of neutrophils through stimulating platelets. We have also demonstrated that the binding between mCRP and platelets might relay on the aa 35-47 of mCRP and the lipid rafts of platelets. In the further study, we intend to investigate the characteristics and the signal pathway of the binding between mCRP and platelets with recombinant mCRP which has mutant aa 35-47. We also intend to investigate the influence of mCRP-activated platelets on the injury of endothelial cells induced by ANCA with flow chamber experiment, laser confocal imaging and in vivo imaging technology. After establishing the AAV rat models, we want to observe the renal protective effects of 1,6-bis(phosphocholine)-hexane, which can inhibit the dissociation form pCRP into mCRP. Our study may help to understand the mechanisms of the pathogenesis of AAV.