CAJ | 학술논문

目的观察他克莫司(FK506)促进神经干细胞(neural stem cels,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T8脊髓,建立压迫型脊髓损伤动物模型.损伤后7 d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1 mg·kg-1·d-1连续7 d腹腔注射FKS06.连续观察1,2,4,8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1.7 cm.诱发电位结果显示,FKS06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.
목적 관찰타극막사(FK506)촉진신경간세포(neural stem cels,NSCs)이식후손상척수신경전도통로수복적작용.방법 현미경하동맥류협압박SD대서T8척수,건립압박형척수손상동물모형.손상후7 d안수궤수자표법분위삼조:대조조,우손상중심정향주사등삼염수;세포이식조,우손상중심정향주사NSCs;FK506조,우손상중심정향주사NSCs,동시안1 mg·kg-1·d-1련속7 d복강주사FKS06.련속관찰1,2,4,8주,통과BBB평분、BDA순행시종、체감유발전위(SEP)여운동유발전위(MEP)감측,비교관찰대서척수신경전도공능적회복정황.결과 상후후지운동공능균유불동정도적회복,4주시회복속도최명현,8주시BBB최고평분가체6분;BDA순행시종,FK506조화세포이식조재1주후유부분신경섬유통과,8주시각조균유부분BDA양성표기적피질척수속재생통과척수손상부위,특별시FK506조가연속지거손상중심1.7 cm.유발전위결과현시,FKS06조재2주시SEP적잠복기즉명현축단(P<0.05).4주후,FK506조MEP잠복기여각조비교명현축단(P<0.05),표명응용면역억제제능촉진NSCs대손상척수적회복,축단SEP화MEP적잠복기,조기대SEP개선명현,후기대MEP개선명현.결론 척수손상대서이식NSCs후,계통응용FK506후구유신경보호화신경영양작용,가가쾌신경전도공능적회복.
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 T8 spinal cord segment of SD 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 intrapernerve 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 8weeks. 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 found crossing the injured center of the spinal cord one week later in FK506 group and cell transplantation group,that BDA-positive labeled corticospinal tract fibets were seen across the injury site in all groups by the end ofthe eight weeks.In the FKS06 group,the regeneration could be observed even as 1.7 cm away from tlle 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 spihal cord,shorten the latency of SEP and MEP，improve SEP at early stage and MEP at late stage．Conclusions Systemic application immuno suppressive agents FK506 plays an important role in neuroprotection and neurotrophy，which promotes the repair of the injured spinal cord after neural stem cell transplantation．