低剂量他克莫司治疗大鼠急性脊髓损伤的实验研究

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。

Experimental study of effect of low-dose tacrolimus on acute spinal cord injury in rats

Objective:To explore the effect of low-dose tacrolimus on acute spinal cord injury(SCI)in rats.Method:A total of 72 male rats were divided randomly into three groups:the sham-operative group(n=12),the injury group(n=30)and the test group(n=30)treated with tacrolimus,while the latter two groups were subjected to SCI at the T10 level with a weight-drop impactor(10g weight was dropped from a 4.0 cm height).The rats in tacrolimus group were injected with tacrolimus 0.3mg/kg 5 minutes after SCI,while the other groups received equivalent amount of 0.9% normal saline likewise.Neurological function,histopathological examination of injured spinal cord and detection of the apoptosis of neural cells by the terminal deoxynucleotidyl transferase-mediated deoxyuredine triphosphate-digoxin nick end labeling(TUNEL)method were assessed at certain time point after SCI.Result:The inclined plate test scores and BBB scales in the tacrolimus group were significantly higher than those in the injured group at 3?7?14?21d after SCI respectively(P<0.05).Hemorrhage and necrosis in injured epicenter of the tacrolimus group were less serious than those of the injury group all time after SCI.The amount of TUNEL-positive cells were significantly less in the tacrolimus group than in the injury groupat 6?24?48?72h after SCI(P<0.05).Conclusion:Low-dose tacrolimus possesses neuroprotective effect on neuron after acute spinal cord injury in rats,which can reduce apoptosis of neural cells,attenuate secondary spinal cord injury and thus improve neurological function recovery.