内皮素受体拮抗剂对损伤脊髓早期保护作用

Protective Effects of Endothelin Receptor Antagonist on Traumatized Spinal Cord in Rats

目的 :评价非选择性内皮素 (ET)受体拮抗剂PD14 5 0 6 5对损伤脊髓的保护作用 ,证实ET参与脊髓损伤 (SCI)后继发损伤的假设并探讨其作用机制。方法 :压迫法致伤大鼠脊髓 (5 0 g ,1min)。损伤前 10min鞘内注射PD14 5 0 6 5或生理盐水 ,观察脊髓血流 (SCBF)、丙二醛 (MDA)、细胞内钙 ([Ca2 +] i)、伊文思兰 (EB)及水含量变化。结果 :伤区SCBF在伤后5min即有明显下降 ,为基线的 (75 .2 3± 9.2 1) % ,2h降为 (5 7.0 6± 7.35 ) % ;伤区邻近血流下降较慢 ,伤后 30min降为 (79.82± 7.98) %。伤区及邻近区伤后 4hSCBF都未恢复。伤段脊髓组织中MDA、[Ca2 +] i、EB和水含量均高于假手术组 (P <0 .0 5 )。PD14 5 0 6 5明显改善了伤区SCBF ,消除了伤区邻近段SCBF的下降。PD14 5 0 6 5预处理组脊髓中MDA、[Ca2 +] i、EB和水含量均低于生理盐水组 (P <0 .0 5 )。结论 :PD14 5 0 6 5对损伤脊髓早期有明显保护作用 ,ET及其受体可能通过多种途径参与SCI后的继发损伤。

Objective: To evaluate the effects of PD145065(non selective endothelin(ET)receptor antagonist)on injured spinal cord and explore mechanisms of how ET plays a role in secondary injury following spinal cord injury(SCI).Methods:Spinal cord of rat was traumatized by compression(50g,1min).PD145065 or vehicle was administered intrathecally 10 minutes before SCI.Alterations of spinal cord blood flow(SCBF),molondialdehyde(MDA),the total content of intracellular calcium([Ca 2+ ] i),Evans blue(EB),and water in spinal cord were inspected.Results:SCBF of injured area decreased obviously 5 minutes after SCI.SCBF was 75.23±9.21% of baseline 5 minutes after SCI,57.06±7.35% 2 hours.SCBF of adjacent area decreased lower.SCBF was 79.82±7.98% of baseline 30 minutes after SCI.SCBF of injured and adjacent areas did not recover 4 hours after SCI.The contents of MDA,[Ca 2+ ] i,EB and water in traumatized spinal cord were significantly more than that of sham( P<0.05 )。PD145065 ameliorated SCBF of injured area obviously and abolished the decrease of SCBF of adjacent area.The contents of MDA,[Ca 2+ ] i,EB and water in spinal cord of PD145065 treated group were significantly less than that of saline treated group( P<0.05 ).Conclusion:PD145065 has protective effects on traumatized spinal cord in early phase.ET and its receptors may play a role in secondary injury following SCI by multiple pathways.ETA/ETB receptor antagonist may be useful in treatment of clinical SCI.