血管紧张素Ⅱ1型受体自身抗体（AT1-AA）是介导子痫前期（PE）发病的关键病因，其产生机制尚不十分清楚。我们预实验发现caspase-1在PE胎盘中表达增强，推测其可能是介导滋养细胞炎性坏死过程中自身抗原暴露进而诱发AT1-AA产生的关键靶标。我们研究证实脂氧素A4（LXA4，炎症“刹车信号”）能够改善大鼠PE症状，并能抑制滋养细胞炎症与凋亡，而LXA4是否能够调控caspase-1抑制AT1-AA产生及PE发病尚不清楚。本项目拟以PE患者和小鼠模型系统研究PE发病过程中AT1-AA与caspase-1和LXA4的相关性；利用基因敲除与siRNA技术证实caspase-1在介导AT1-AA产生及PE发病中的作用；利用PE小鼠模型，滋养细胞及共培养模型探索LXA4通过caspase-1对AT1-AA产生及PE发病的调控机制。旨在进一步阐明PE的发病机制，也为治疗PE提供理论依据和关键靶标。

Angiotensin II type 1 receptor autoantibody (AT1-AA) is a key cause of preeclampsia (PE) onset, but the mechanism of AT1-AA production has not been revealed. Our previous results confirmed that caspase-1 is up-regulated in PE placenta. It’s speculated that caspase-1 may represent the key target in mediating self-antigen exposure for inducing AT1-AA production in trophoblast inflammatory necrosis. We found previously that lipoxin A4 (LXA4, "brake signal" of inflammation) could improve PE-related symptoms in rats, and inhibit the inflammation and apoptosis of trophoblast. However, it’s unclear whether LXA4 could inhibit AT1-AA production and PE development by modulating caspase-1. The project will first study the relationship between AT1-AA and caspase-1 and LXA4 in PE development by employing PE patients and mice model. Moreover, we will study the roles of caspase-1 in mediating AT1-AA production and PE development by employing gene knockout and siRNA of caspase-1. We will further study whether LXA4 inhibits AT1-AA production and PE development by regulating caspase-1 by employing PE mice model, trophoblast and co-culture model. The project aims to further elucidate the pathogenesis of PE, and provide theoretical basis and key targets for PE treatment.