So A
Service de rhumatologie, médecine physique et rééducation, Département de médecine CHUV, 1011 Lausanne.
Rev Med Suisse. 2007 Mar 21;3(103):720, 722-4.
Gout is due to the formation and tissue deposition of MSU crystals. Hyperuricemia promotes crystal formation and results from the disequilibrium between the synthetic and elimination rates of uric acid. Recent studies have elucidated the mechanisms of renal handling of uric acid by specific transporters (URATI and OAT) which play a role in uric acid excretion. MSU crystals provoke inflammation by activating leukocytes to produce inflammatory cytokines. One mechanism is through the TLR2 and TLR4 receptors, which form part of the innate immune system. MSU crystals can also activate a protein complex called the inflammasome, which in turn activates IL-1 processing to yield the secreted mature form of IL- 1beta. The inflammatory effects of MSU can be blocked by IL-1 inhibitors. These advances could provide new targetted therapeutic approaches to treat hyperuricemia and gout.
痛风是由于单钠尿酸盐(MSU)晶体的形成和组织沉积所致。高尿酸血症促进晶体形成,其源于尿酸合成与排泄速率之间的失衡。最近的研究阐明了特定转运蛋白(URATI和OAT)对尿酸进行肾脏处理的机制,这些转运蛋白在尿酸排泄中发挥作用。MSU晶体通过激活白细胞产生炎性细胞因子来引发炎症。一种机制是通过Toll样受体2(TLR2)和Toll样受体4(TLR4),它们是固有免疫系统的一部分。MSU晶体还可激活一种名为炎性小体的蛋白复合物,炎性小体继而激活白细胞介素-1(IL-1)的加工过程,产生分泌型成熟白细胞介素-1β(IL-1β)。MSU的炎性作用可被IL-1抑制剂阻断。这些进展可为治疗高尿酸血症和痛风提供新的靶向治疗方法。