Role of neuropeptide, substance-p, on the mechanisms of joint destruction in rheumatoid arthritis.

临床证据表明，周围神经系统可能参与炎症的病理生理过程。神经肽P物质（SP）存在于外周感觉神经的无髓C纤维中，是慢性炎症的可能介质之一，因为它在炎症关节中被检测到，对间充质细胞有多种生物学作用。还报道了SP诱导从类风湿性关节炎患者获得的滑膜细胞的胶原酶释放。然而，SP是否直接诱导关节软骨降解仍不清楚。因此，我们研究了SP对体外培养的牛关节软骨细胞基质金属蛋白酶释放和硫酸化糖胺聚糖积累的影响，结果表明，外源性SP可增加单层培养的牛关节软骨细胞基质金属蛋白酶的释放。在10 μ M浓度下孵育48小时，观察到显著增加（p&lt;0.05）<-9>。同时SP对关节软骨细胞合成硫酸化糖胺聚糖无影响。提示SP可能通过增加炎症性关节炎时基质金属蛋白酶的释放而加重关节软骨的退化。

Clinical evidences have suggested that the peripheral nervous system might be involved in the pathophysiology of inflammation. The neuropeptide substance P (SP), which has been found in unmyelinated C fiber of the peripheral sensory nerve, is reported to be one of the possible mediators of chronic inflammation, since it has been detected in inflamed joints and has various biological effects on mesenchymal cells. It is also reported that SP induced collagenase release of synoviocytes obtained from patients with rheumatoid arthritis. However, whether or not SP induces articular cartilage degradation directly, remains unknown. Therefore we have investigated the effect of SP on matrix metalloproteinase release and the accumulation of sulfated glycosaminoglycan of the articular chondrocyte in vitro.Administration of exogenous SP resulted in the increase of metalloproteinase release in the monolayr cultured bovine articular chondrocytes. Significant increase (p<0.05) was observed at the concentration of 10^<-9> M for 48h incubation. Meanwhile SP had no effect on sulfated glycosaminoglycan synthesis of the articular chondrocyte. These results suggest that SP may increase the deterioration of articular cartilage through augmentation of the release of metalloproteinase in inflammatory arthritis.