脊髓CGRP在大鼠实验性关节炎形成和发展中的作用

The Effects of CGRP at Spinal Level on the Development of Experimental Arthritis in Rat

采用鞘内注射降钙素基因相关肽（ＣＧＲＰ）受体拮抗剂人ＣＧＲＰ片段８－３７（ｈＣＧＲＰ８－３７），探讨了佐剂性关节炎大鼠初级感觉系统中ＣＧＲＰ增多的意义。结果：佐剂前注射ｈＣＧＲＰ８－３７的动物，在注射佐剂后１～２０ｄ，患肢及健肢皮温均高于对照组（Ｐ＜０．０５）；患肢足容积明显大于对照组（Ｐ＜０．０５），并且在形成变态反应性佐剂性关节炎时（佐剂后１３～２０ｄ），健肢足容积也明显增加（Ｐ＜０．０５）；但双后肢的痛阈变化与对照组相比没有明显差异（Ｐ＞０．０５）。上述结果表明，佐剂前鞘内注射ｈＣＧＲＰ８－３７，使急性关节炎和多发性关节炎均有所加重。佐剂后１２ｄ注射ｈＣ－ＧＲＰ８－３７的动物，双后肢的肿胀积分均明显高于对照组（佐剂后１８～５０ｄ，Ｐ＜０．０５或０．０１），痛级别也明显高于对照组（佐剂后１４～５０ｄ，Ｐ＜０．０１），但痛阈的变化不明显（Ｐ＞０．０５）。因此佐剂后１２ｄ鞘内注射ＣＧＲＰ的拮抗剂也可加重关节炎的炎症反应。这进一步证明了脊髓ＣＧＲＰ可能具有抗炎和抑制免疫反应的作用。

further investigate the significance of the increased CGRP in spinal dorsal horn and primary sensory neurons in arthritic rats,the effects ofintrathecal injection of hCGRP 8 37 ,an antagonist of CGRP receptor,on the development of arthritis were examined by using behavioral tests An intrathecal injection of hCGRP 8 37 prior to FCA or on day12,blocked(reversed)the action of CGRP,could potentiate the symptoms such as swelling,ong oing pain,redness and hotness in the injected limbs and facilitate the development of the delayed polyarthritis. The observations furt her in dicate that the increase of CGRP in the primary sensory system may play an antiinflammatory role with the immunity tobe inhibited via anegative feedback regulation.