内皮素受体拮抗剂对损伤脊髓早期保护作用

目的评价非选择性内皮素(ET)受体拮抗剂PD145065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(50g,1min)。损伤前10min鞘内注射PD145065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(75.23±9.21)%，2h降为(57.06±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4h?SCBF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＜0.05)。PD145065明显改善了伤区SCBF，消除了伤区邻近段SCBF的下降。PD145065预处理组脊髓中MDA、［Ca2+］i、EB和水含量均低于生理盐水组(P＜0.05)。结论PD145065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。临床应用ET受体拮抗剂对SCI可能有治疗作用。

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

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(［Ca2+］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,［Ca2+］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,［Ca2+］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.