脂氧素A4（LXA4）因强烈的抗炎症作用被称为"炎症刹车剂"。我们前期研究证实给予外源性LXA4可抑制重症胰腺炎（SAP）局部炎症，减轻过度的全身炎症反应（SIRS），缓解肺损伤，改善预后。但LXA4半衰期短，多于炎症晚期产生，SAP炎症早期少量的LXA4对于此迅速发展为SIRS的疾病难起逆转作用。鉴此，我们设想"将LXA4合成的关键酶（15-LO）基因导入胰腺腺泡细胞，重组构建的启动子系统能使LXA4在炎症早期过度产生；从而抑制SAP炎症，负调控SIRS进展"。本课题借助基因转染技术和转基因动物，使15-LO在SAP启动早期表达，可研究LXA4对局部炎症及SIRS激活的调控，并评价此策略对胰外脏器的保护作用。我们首次尝试将LXA4合成的关键酶在炎症早期启动过表达，对局部炎症进行调控，并试图下调SIRS，改善脏器损伤。该课题不仅为SAP防治提供新思路，尤其突出了对SIRS的负调控。

Lipoxin A4 (LXA4) is called "inflammatory braking signal" for its remarkable anti-inflammatory effect. Our pilot studies also confirmed that LXA4 could improve prognosis of severe acute pancreatitis (SAP) by restraining local inflammation, reducing excessive Systemic Inflammatory Response Syndrome (SIRS), and ameliorating lung injury. However,LXA4 is mainly generated in the late stage of inflammation and the half-time is short . The quantity of LXA4 produced in the early stage is so little that it could hardly reverse the SIRS in SAP which developed promptly. Accordingly, we assume that to increase LXA4 synthesis in early stage of SAP by transfecting 15-lipoxygenase(15-LO), the key enzyme in LXA4 biosynthesis, to pancreatic acinar cells, could further inhibit the progress of inflammation and negatively regulate SIRS. Taking the advantage of genetic technology and transgenic animals, our subject aimed to overexpress 15-LO in the pancreas in the early stage of SAP. The effects of LXA4 on local inflammation and the mechanism of regulating SIRS activation and protecting the remote organ injury in SAP will be studied. It is the first study to regulate SIRS by promoting the expression of LXA4 in pancreas in the early stage of SAP, secondary to attend to control local inflammation, thus alleviating the remote organ injury. Our research not only provides novel ideas for the treatment of SAP, but also emphasizes the regulation of SIRS.