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

甘丙肽样肽(GALP)是在寻找孤儿受体配体时发现的。GALP存在于下丘脑弓状核，但GALP与慢性关节炎的关系尚不清楚。基于这种情况，本研究的目的是探讨GALP对慢性应激，特别是对实验性关节炎的影响。实际上，我们不仅研究了GALP基因在急性应激刺激(渗透压刺激和内毒素注射)中的表达，也研究了GALP基因在慢性炎性应激刺激(佐剂性关节炎)中的表达。结果，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基因表达有较强的刺激作用。慢性炎症应激时GALP基因表达增加可能受前列腺素系统的调节。很久以前，除了典型的关节畸形和炎性改变外，关于类风湿关节炎患者慢性炎性应激引起的中枢神经系统的各种改变也有报道。几乎所有的生理反应机制都还不清楚。然而，类风湿性关节炎这一外周慢性炎症性疾病的发病机制仍需进一步探讨中枢神经系统尤其是下丘脑的影响。

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.