AEP小分子抑制剂compound#11对小鼠脊髓损伤的修复作用

目的 研究天冬酰胺内肽酶(asparagine endopeptidase, AEP)小分子抑制剂compound#11对小鼠脊髓损伤的修复作用。方法 采用改造动脉夹制作小鼠脊髓损伤钳夹模型。28只健康雌性C57BL/6小鼠随机分为compound#11干预组、丙戊酸（valproic acid，VPA）干预组、生理盐水对照组、假手术组，每组7只。术后7、14、21、28d，对各组小鼠进行BMS评分、Rotarod检测，评价小鼠后肢运动功能。通过H-E染色和免疫荧光染色观察各组小鼠脊髓组织的病理变化。采用运动诱发电位评价脊髓损伤后脊髓传导功能的完整性。结果 compound#11干预组、VPA干预组小鼠与生理盐水对照组相比后肢运动功能恢复更好（P＜0.05）；组织学检测显示，相对于生理盐水对照组，compound#11干预组、VPA干预组小鼠胶质细胞增生及疤痕面积更小，神经元凋亡数目更少；电生理检测显示，compound#11干预组、VPA干预组、生理盐水组均呈现延长期波幅逐渐增加，潜伏期缩短趋势，且组间差异无统计学意义（P>0.05）。结论 单独使用compound#11修复脊髓损伤，具有一定的改善趋势，但其药用效价有待进一步提升。
Objective To investigate the effect of AEP small molecule inhibitor compound #11 on repairing of spinal cord injury in mice. Methods Twenty-eight healthy female C57BL/6 mice were equally divided into 4 groups: compound #11 group, VPA group, saline control group and sham operation group. Spinal cord injury was induced by modified arterial clamp method in all groups except sham operation group. The compound #11, valproic acid and normal saline were given by intraperitoneal injection in compound #11, VPA and saline control groups, respectively. BMS scores and Rotarod scores were evaluated at 7, 14,21 and 28 days after operation. The spinal cord tissue samples were taken for H-E staining and immunofluorescence staining. The integrity of spinal cord conduction function was assessed by motor evoked potential. Results Compared with saline control group, the motor function recovery was better in mice of compound#11 group and VPA group (P＜0.05). The proliferation of glial cells, the scar formation and apoptosis of neuronal cells in compound#11 group and VPA group were less marked than those in saline control group. The electrophysiological examination showed that the amplitude of compound#11 group, the VPA group, saline group were increased gradually, the latency was shortened, but there were no significant differences among three groups. Conclusion Compound #11 alone may have certain effect in repair of spinal cord injury, but the efficacy need to be further improved