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Clarification of new brain peptide's pathophysiologic role and molecular mechanism in arthritic animal model.

阐明新脑肽在关节炎动物模型中的病理生理作用和分子机制。

基本信息

批准号：
16591518
负责人：
OHNISHI Hideo
金额：
$ 1.92万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Galanin-like peptide (GALP) was found from searching for orphan receptor ligands. GALP is exists in the hypothalamic arcuate nucleus, however, there is no knowledge about its relationship between GALP and chronic arthritis. On the basis of these circumstances, the purpose of this study was to investigate influence of GALP for chronic stress particularly in experimental arthritis. Practically, we evaluated GALP gene expression not only in acute stress stimulation (osmotic challenge and LPS injection), but also in chronic inflammatory stress stimulation (adjuvant arthritis). In result, we clarified following facts. GALP gene expression at the arcuate nucleus neuron was dependent on leptin and regulated by blood sugar control caused by insulin administration. Osmotic challenge has a potent stimulation for influence in GALP gene expression at posterior pituitary cells. Increase of the GALP gene expression in chronic inflammatory stress was possibly regulated by prostaglandin system. Long before, various change of central nervous system based on chronic inflammatory stress in patients with rheumatoid arthritis has been reported in addition to typical joint deformity and inflammatory change. Almost various mechanisms in physiological reaction are still unknown. However, we have to evaluate furthermore about the influence of central nervous system especially hypothalamus in pathogenesis of rheumatoid arthritis which is peripheral chronic inflammatory disease.

甘丙肽样肽（Galanin-like peptide，GALP）是在寻找孤儿受体配体的过程中发现的。GALP存在于下丘脑弓状核，但其与慢性关节炎的关系尚不清楚。在此基础上，本研究的目的是探讨GALP对慢性应激尤其是实验性关节炎的影响。实际上，我们不仅在急性应激刺激（渗透压挑战和LPS注射），而且在慢性炎症应激刺激（佐剂性关节炎）评估GALP基因表达。因此，我们澄清了以下事实。GALP基因在弓状核神经元的表达依赖于瘦素，并受胰岛素给药引起的血糖控制的调节。渗透压刺激对垂体后叶细胞GALP基因表达有明显的影响。慢性炎症应激时GALP基因表达增加可能受前列腺素系统调节。长期以来，除了典型的关节畸形和炎性改变外，类风湿关节炎患者还报告了基于慢性炎症应激的中枢神经系统的各种改变。生理反应中的各种机制几乎都是未知的。然而，中枢神经系统尤其是下丘脑在类风湿关节炎这一外周慢性炎症性疾病发病机制中的作用有待进一步研究。