K506促进神经干细胞移植后损伤脊髓神经传导通路的修复

FK506 promotes repair of injured spinal cord pathway after neural stem cell transplantation

目的观察他克莫司（FK506）促进神经干细胞（neuralstem cells，NSCs）移植后损伤脊髓神经传导通路修复的作用。方法显微镜下动脉瘤夹压迫sD大鼠L脊髓，建立压迫型脊髓损伤动物模型。损伤后7d按随机数字表法分为三组：对照组，于损伤中心定向注射等渗盐水；细胞移植组，于损伤中心定向注射NSCs；FK506组，于损伤中心定向注射NSCs，同时按1mg·kg^-1·d^-1连续7d腹腔注射FK506。连续观察I，2，4，8周，通过BBB评分、BDA顺行示踪、体感诱发电位（SEP）与运动诱发电位（MEP）监测，比较观察大鼠脊髓神经传导功能的恢复情况。结果伤后后肢运动功能均有不同程度的恢复，4周时恢复速度最明显，8周时BBB最高评分可达6分；BDA顺行示踪，FK506组和细胞移植组在1周后有部分神经纤维通过，8周时各组均有部分BDA阳性标记的皮质脊髓束再生通过脊髓损伤部位，特别是FK506组可延续至距损伤中心1．7cm。诱发电位结果显示，FK506组在2周时SEP的潜伏期即明显缩短（P〈0．05）。4周后，FK506组MEP潜伏期与各组比较明显缩短（P〈0．05），表明应用免疫抑制剂能促进NSCs对损伤脊髓的恢复，缩短SEP和MEP的潜伏期，早期对SEP改善明显，后期对MEP改善明显。结论脊髓损伤大鼠移植NSCs后，系统应用FK506后具有神经保护和神经营养作用，可加快神经传导功能的恢复。

Objective To observe the effect of tacrolimus （FK506） in promoting repair of the injured spinal cord pathway after neural stem cell transplantation in rats. Methods A neurysm clip was used to compress the Ts spinal cord segment of SI） rats under microscope to establish model of spinal cord injury. The rats were randomly divided into three groups seven days after injury, ie, control group （ injection of normal saline at the injury center） , transplantation group （ injection of neural stem cells, NSCs, at the injury center）, FK506 group （ injection of NSCs at the injury center plus 7 days of intraperitoneal injection of immunosuppressant FKS06 at 1 mg·kg^-1·d^-1 ）. The recovery of the rat spinal cord nerve conduction was compared by using the Basso-Beatfle-Bresnahan （BBB） scale, BDA tracing, somatosensory evoked potential （SEP） and motor evoked potentials （MEP） monitoring at 1, 2, 4 and 8 weeks. Results The motor function of the hind limb after injury was recovered in various degrees with time, with the most significant recovery at 4 weeks. The BBB score reached 6, the maximum at 8 weeks. BDA tracing showed that some nerve fibers were foumJ crossing the injured center of the spinal cord one week later in FK506 group and cell transplantation grcup, that BDA-positive labeled corticospinal tract fibers were seen across the injury site in all groups by the end of the eight weeks. In the FK506 group, the regeneration could be observed even as 1.7 cm away from the injury center. SEP latency was significantly shorter in the FK506 group after two weeks （ P 〈 0.05 ） and the MEP latency in the FK506 group was shortened significantly at four weeks compared with the other groups （ P 〈 0.05 ）, indicating that the immunosuppressants could promote the recovery of the injured spinal cord, shorten the latency of SEP and MEP, improve SEP at early stage and MEP at late stage. Conclusions Systemic application immunosuppressive agents FK506 plays an important role in neuroprotection and neurotrophy, which promotes the repair of the injured spinal cord after neural stem cell transplantation.