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目的:探讨低剂量他克莫司(tacrolimus,又名FK506)对大鼠急性脊髓损伤是否具有神经保护作用。方法:雄性Wistar大鼠72只,随机分为假手术组(12只)、损伤组(30只)和FK506治疗组(30只)。采用Allen’s打击法致伤大鼠T10脊髓,假手术组仅做椎板切除术。FK506治疗组在脊髓损伤后5min一次性经尾静脉注射FK5060.3mg/kg,其余两组以相同方法给予等量生理盐水。致伤后30min、6h、24h、48h、72h取伤段脊髓组织行病理观察及原位末端标记法(TUNEL)检测神经细胞凋亡,伤后1、3、7、14、21d行脊髓功能BBB评分和斜板实验。结果:伤后3、7、14、21d,FK506治疗组斜板实验和BBB评分明显优于损伤组,两组间比较差异有显著性(P<0.05);伤后各时间点FK506治疗组脊髓损伤区出血坏死较损伤组轻;伤后6、24、48、72h神经细胞凋亡FK506治疗组较损伤组明显减少,两组间比较差异有显著性(P<0.05)。结论:在大鼠急性脊髓损伤后早期应用低剂量他克莫司(0.3mg/kg)治疗对神经具有保护作用,可减少神经细胞凋亡,减轻脊髓继发性损伤,促进脊髓功能恢复。
Objective: To investigate whether low dose tacrolimus (aka FK506) has neuroprotective effect on acute spinal cord injury in rats. Methods: Seventy two male Wistar rats were randomly divided into sham operation group (n = 12), injury group (n = 30) and FK506 treatment group (n = 30). Allen’s hit method was used to injure rat T10 spinal cord. Sham operation group was only laminectomy. In the FK506 group, FK5060.3mg / kg was injected into the caudal vein five minutes after the spinal cord injury, and the other two groups were given the same amount of normal saline in the same way. The injured spinal cord tissues were harvested at 30 min, 6 h, 24 h, 48 h, 72 h after injury and the apoptosis of spinal cord was detected by TUNEL. The spinal cord function BBB Scoring and Ramp Experiment. Results: At 3, 7, 14 and 21 days after injury, the skeletal plate test and BBB score of FK506 treatment group were significantly better than those of injury group (P <0.05). The spinal cord of FK506 treatment group The hemorrhage and necrosis in the injury area was lighter than that in the injury group. The apoptosis of neurons in FK506 group was significantly decreased at 6, 24, 48 and 72 hours after injury compared with the injury group. There was significant difference between the two groups (P <0.05). Conclusion: The early application of low dose of tacrolimus (0.3mg / kg) after acute spinal cord injury in rats can protect the nerve, reduce the apoptosis of nerve cells, reduce secondary spinal cord injury and promote the recovery of spinal cord function.