大剂量强啡肽A_(1-17)对脊髓NMDA受体功能和一氧化氮合酶活性的影响

Effects of High Dose of Dynorphin on NMDA Receptor and NOS Activities in Spinal Cord of Rats

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-

Objective To elucidate the effects of NmethylDaspartate(NMDA)receptor and nitric oxide synthase (NOS) activity in dynorphin (Dyn)induced spinal cord injury. Methods The NMDA receptor activity was measured by radioligand of 3HMK801.The constitutive and inducible NOS (cNOS and iNOS) activities were assayed by 3Harginine conversion. Results In ventral samples, both 3HMK801 binding and cNOS activity increased at 05 h and persisted for 48 h while iNOS activity enhanced at 4 h after intratheacal injection (i.t.) Dyn A (117) at dose of 20 nmol/L. However, the 3HMK801 binding activity reduced significantly from 4 h to 24 h and cNOS activity did not change at the same time in dorsal samples. 7nitroindozol (7NI) and aminoguanidine (AG) inhibited the effects of Dyn A (117) (20 nmol/L) on 3HMK801 binding and NOS activities in ventral samples. NnitroLarginine methyl ester (LNAME) did not affect the elevation of Dyn A (117) on NOS activities but caused 3HMK801 binding activity reduction in ventral samples. Conclusions NMDANOS pathway might play important role in Dyn spinal neurotoxicity. NOS inhibitors and Dyn might produce cooperative downregulation on the function of NMDANOS pathway in dorsal cord.