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目的 观察大剂量强啡肽 A( 1 - 1 7) (dynorphin,Dyn)以及一氧化氮合酶 (NOS)抑制剂对脊髓NMDA受体功能和 NOS活性的影响。方法 以 3H- MK80 1为配基 ,采用放射配基法测定 NMDA受体结合活性 ;以精氨酸转化法测定脊髓组织胞浆相 NOS活性。结果 给大鼠蛛网膜下腔注射 Dyn A( 1 - 1 7)0 .5 h后 ,脊髓腹侧组织的 3H- MK80 1结合活性以及 c NOS活性即显著升高 ,且持续 48h;i NOS在给药后 4h升高。脊髓背侧 3H- MK80 1结合活性在给药后 4h开始下降 ,48h恢复正常 ,背侧 c NOS活性无明显变化。预先蛛网膜下腔注射 ne NOS抑制剂 7-硝基吲哚和 i NOS抑制剂氨基胍可对抗 Dyn的致瘫作用 ,同时对抗脊髓腹侧 NMDA受体结合活性及 c NOS、i NOS活性的升高。结论 脊髓腹侧 NMDA受体功能和 NOS活性增高可能与 Dyn致瘫作用有关。NOS抑制剂可对抗 Dyn的致瘫作用 ,并且与 Dyn协同下调脊髓背侧 NMDA- NOS通路的功能
Objective To observe the effects of high dose of dynorphin (Dyn) and nitric oxide synthase (NOS) inhibitor on NMDA receptor function and NOS activity in the spinal cord. Methods 3H-MK80 1 was used as ligand. The binding activity of NMDA receptor was determined by radioligand. The activity of NOS in spinal cord was measured by arginine transformation. RESULTS: 3H-MK80 1 binding activity and c-NOS activity in the ventral spinal cord tissue of rats were significantly increased after Dyn A (1 - 1 7) 4h after administration increased. The binding activity of 3H-MK80 1 in the dorsal spinal cord began to decline at 4h after administration and returned to normal at 48h. There was no significant change in c NOS activity on the dorsal side. The pre-subarachnoid injection of ne-NOS inhibitor 7-nitroindole and iNOS inhibitor aminoguanidine can antagonize Dyn-induced paralysis, while antagonizing the spinal cord ventral NMDA receptor binding activity and c NOS, i NOS activity increased high. Conclusion The increase of NMDA receptor function and NOS activity in the ventral spinal cord may be related to the paralysis induced by Dyn. NOS inhibitors antagonize the paralysis induced by Dyn and co-act with Dyn to down-regulate the function of the NMDA-NOS pathway in the dorsal spinal cord