甘草甜素修复小鼠坐骨神经损伤的研究

Effects of glycyrrhizin on repairing sciatic nerve injury in mice

目的探讨甘草甜素治疗BALB／c小鼠坐骨神经损伤模型的疗效。方法建立小鼠右侧坐骨神经损伤模型，随机分为对照组及甘草甜素低、中、高剂量组。术后第4、8周测定各组小鼠坐骨神经功能指数（SFI），术后第1天、第1、2、4、8周切取患侧脊髓（L4～L6段），行Western blot分析和实时定量聚合酶链反应（Real—time PCR），检测生长相关蛋白43（GAP-43）和p75神经营养因子受体（p75NTR）蛋白及mRNA表达水平。结果各组术后SFI值均逐渐恢复，治疗组SFI显著优于对照组：高、中、低、对照组SFl分别为：术后4周：61．300±1．319、63．1804-1．030、68．680±0．653、72．108±0．823；术后8周：41．440±0．373、46．210±0．747、50．830±0．866、61．350±1．123。高、中、低剂量组与对照组比较，术后4周：t=16．560、16．504、8．485，术后8周：t=37．581、25．088、16．577，均P=0．000。各组坐骨神经损伤同侧的L4～L6脊髓节段中，术后第1、2、4、8周各剂量组GAP-43蛋白及mRNA表达均显著高于对照组。高、中、低剂量组GAP-43mRNA表达量与对照组比较，术后1周：t=114．858、110.170、12．810；术后2周：t=122．115、63．360、30．745；术后4周：t=28．027、20．757、15．967；术后8周：t=33．467、27．828、12．513；均P=0．000。术后各时间点治疗组p75NTR蛋白及mRNA表达均显著低于对照组，高、中、低剂量组p75NTRmRNA表达量与对照组比较，术后1周：t=55．937、33．212、12．364；术后2周：t=41．779、29．553、14．953；术后4周：t=37．000、22．638、18．198；术后8周：t=42．345、26．800、20．250；均P=0．000。结论甘草甜素能促进小鼠坐骨神经损伤的神经再生，促进小鼠运动功能恢复，其机制可能与增加相应神经脊髓节段GAP-43表达及降低p75NTR表达有关。

Objective To investigate the effects of glycyrrhizin on repairing sciatic nerve injury in BALB/c mice. Methods After mouse sciatic nerve injury model was constructed, the mice were randomly divided into 4 groups ： control group, low - dose glycyrrhizin group, middle - dose glycyrrhizin group, and high -dose glycyrrhizin group. At 4th and 8th week after sciatic nerve injury, functional outcome measure- ments were evaluated by the sciatic functional index （SFI）. At 1 st day, 1 st, 2nd, 4th, and 8th week after sciatic nerve injury, spinal cord （L4- L6） at injured side was cut to perform Western blotting and real - time quantitative polymerase chain reaction （ Real - time PCR）. The protein and mRNA levels of growth associated protein 43 （GAP- 43） and p75 neurotrophic receptor （p75NTR） were detected. Results SFI values were gradually restored after the surgery, SFI values in treatment groups were significantly better than in control group. SFI mean values in high - , middle - , low - dose and control groups were respectively 61. 300±1.319, 63. 180±1.030, 68. 680 ±0.653, 72. 108 ±0.823 （4th week）, 41. 440 ± 0.373,46.210 ± 0.747, 50. 830 ±0.866, 61. 350 ±1.123 （8th week）. SFI values in high -, middle - , low- dose groups compared with in control group, t values were respectively 16. 560, 16. 504, 8.485 （4th week） , 37. 581, 25. 088, 16. 577 （8th week） after surgery. P values were all 0. 000. In the spinal cord （L4 -L6） at the same side of the injured sciatic nerve, the protein and mRNA expressions of GAP -43 were significantly increased in the treatment groups, mRNA expressions of GAP- 43 in high - , middle-, low- dose groups compared with in control group, t values were respectively 114.858,110. 170, 12. 810 （ 1st week） ; 122. 115, 63. 360, 30. 745 （2nd week） ; 28. 027, 20. 757, 15. 967 （4th week） ; 33. 467, 27. 828, 12. 513 （8th week）. P values were all 0. 000. The protein and mRNA expressions of p75NTR were significantly decreased in the treatment groups, mRNA expressions of p75NTR in high - , middle - , low - dose groups compared with in control group, t values were respectively 55. 937, 33. 212, 12. 364 （lst week）; 41. 779, 29. 553, 14. 953 （2nd week）; 37. 0013, 22. 638, 18. 198 （4th week） ; 42. 345, 26. 800, 20. 250 （8th week）. P values were all 0. 000. Conclusion Glyeyrrhizin treatment can promote the regeneration of mouse sciatic nerve injury and recovery of motor function, which may be associated with the increase of GAP-43 expression and the decrease of p75NTR expression in the corresponding nerve tissues.