雷帕霉素促进大鼠坐骨神经急性损伤后神经再髓鞘化和运动功能恢复

The promoting effects of rapamycin on the recovery of regeneration and motor function in rats with periphery injury

目的观察雷帕霉素对大鼠坐骨神经急性损伤后神经再髓鞘化和运动功能的影响。方法采用随机数字表法，将36只成年无特定病原体（SPF）级SD大鼠随机分成两组（n=18）：手术对照组：建立坐骨神经损伤模型后，每天腹腔注射等量生理盐水，连续7d；雷帕霉素组：建立坐骨神经损伤模型后，每天腹腔注射1mg／kg雷帕霉素，连续7d。坐骨神经损伤模型建立后7、14、21d分别测量大鼠运动功能、神经轴突直径与神经纤维总直径的比值（g-ratio值）和透射电镜下坐骨神经自噬泡数目。结果坐骨神经损伤模型建立后7、14、21d，雷帕霉素组自噬泡数目为（8．78±0．55）、（8．33±0．53）、（7．00±0．44）个，明显大于手术对照组[（7．11±0．51）、（6．44±0．44）、（5．56±0．38）个，P=0．041、0．015、0．024]。坐骨神经损伤模型建立后14、21d雷帕霉素组g-ratio值为0．64±0．02、0．60±0．02，明显小于手术对照组的0．744±0．03、0．694±0．02（P=0．014、0．013）。坐骨神经损伤模型建立后14、21d Catwalk测量，雷帕霉素组大鼠术肢接触平均面积[（1．604±0．04）、（2．26±0．04）cm。]和接触平均压力值（CMI）（67．96±2．28、76．79±1．30）均明显大于手术对照组肢接触平均面积[（1．47±0．03）、（2．09±0．06）cm^2]及接触平均压力值（58．14±1．78、70．07±1．17，P=0．018、0．036和P=0．007、0．003），坐骨神经损伤模型建立后7d两组g-ratio值与Catwalk测量的术肢接触平均面积、CMI值差异均无统计学意义。结论雷帕霉素促进大鼠坐骨神经急性损伤后神经再髓鞘化和运动功能恢复。

Objective To observe the effects of rapamycin on the recovery of regeneration and motor function in the rats with periphery injury. Methods Thirty-six specific pathogen free （SPF） female SD rats were randomly divided into 2 groups, 18 rats in each group. Operative control group was intraperitoneally injected with saline in the same volume once a day for 7 days after sciatic nerve crush injury （SCI）. Rapamycin group was intraperitoneally injected at a dose of 1 mg/kg rapamycin once a day for 7 days after SCI. The motor function was measured by Catwalk XT machine, and g-ratio and the number of the autophagic structures were measured by electron microscope at 7th, 14th, 21st day respectively after SCI. Results The number of the autophagie structures in rapamycin group was 8.78±0. 55, 8. 33±0. 53, 7.00±0. 44 at 7th, 14th, 21st day respectively after SCI, significantly greater than 7.11±0. 51, 6.44±0.44 and 5.56±0.38 in operative control group correspondingly （P =0.041,0.015,0.024）. The g-ratio value in rapamycin group was 0.64±0.02 and 0.60±0.02 at 14th, 21st day respectively after SCI, significantly lower than 0. 74±0.03 and 0. 69±0.02 in operative control group correspondingly （ P=0.014, 0.013）. The contact mean areas [ （1.60±0.04）, （2. 26±0. 04） cm^2] and contact mean intensity （CMI） （67.96±2.28 and 76. 79±1.30） in rapamyein group at 14th and 21st day respectively after SCI were significantly higher than the contact mean areas [ （ 1.47±0.029 ）, （ 2.09±0.06） cm^2 ] , and CMI （58.14±1.78 and 70.07±1.17） in operative control group correspondingly （P =0.018, 0.036 and P = 0.007, 0.003 ）. There were no significant differences in g-ratio value, the contact mean areas and CMI value at 7th day after SCI between two groups. Conclusion Rapamycin promotes the recovery of remyelination and motor function of periphery nerves in rats with SCI.