Urocortin promotes the development of vasculitis in a rat model of thromboangiitis obliterans via corticotrophin-releasing factor type 1 receptors

作者：Xu Youhua; Zhang Rongjian; Chen Jie; Zhang Qichun; Wang Juejin; Hu Jue; Guan Xiaowei; Jin Lai; Fu Hong; Gui Bo; Guo Yuanyuan; Li Shengnan^*

来源：British Journal of Pharmacology, 2009, 157(8): 1368-1379.

DOI：10.1111/j.1476-5381.2009.00210.x

• Urocortin
• thromboangiitis obliterans
• vasculitis
• CRF(1)-receptor
• CRF(2)- receptor

Background and purpose:
Urocortin is a locally expressed pro-inflammatory peptide. Here we have examined the effects of urocortin on sodium laurate-induced peripheral arterial vasculitis in rats, modelling the mechanisms of thromboangiitis obliterans (TAO).
Experimental approach:
Peripheral vasculitis in rats was induced by sodium laurate and graded by gross appearance on the 12th day after injection. Histological changes in rat femoral arteries were assessed by histopathology and transmission electron microscopy. Blood cell counts, blood rheology, blood coagulation and plasma urocortin, thromboxane B(2), prostaglandin E(2) and soluble intercellular adhesion molecule-1 levels were measured. Expression of urocortin, corticotrophin-releasing factor (CRF(1/2)) receptors, cyclooxygenase (COX)-2 and intercellular adhesion molecule-1 (ICAM-1) at both mRNA and protein levels were determined by RT-PCR and Western blot.
Key results:
Rats showed grossly visible signs and symptoms of TAO on the 12th day after sodium laurate injection. In these rats, blood was in a hypercoagulable state; plasma urocortin, prostaglandin E(2) and soluble intercellular adhesion molecule-1 levels were elevated; and the expression of urocortin, CRF(1) and CRF(1 alpha)-receptors, COX-2 and ICAM-1 in rat femoral arteries were markedly increased. Exogenous urocortin, given for 12 days after sodium laurate, exacerbated the hypercoagulable state and augmented expression of CRF(1 alpha)-receptors, COX-2 and ICAM-1. These effects were abolished by a CRF(1)-receptor antagonist, NBI-27914, or a non-selective CRF-receptor antagonist, astressin, but not by the CRF(2)-receptor antagonist, antisauvagine-30, given with exogenous urocortin.
Conclusion and implications:
Urocortin exacerbated the hypercoagulable state and vasculitis in a model of TAO induced by sodium laurate in rats, via CRF(1)-receptors. COX-2 and ICAM-1 might also have contributed to this exacerbation.

• 出版日期2009-8
• 单位南京医科大学