免疫抑制剂在大鼠坐骨神经损伤修复中的作用

Immunosuppressants impact on rat sciatic nerve injury and repair

目的探讨使用多种免疫抑制剂对大鼠坐骨神经损伤修复后神经轴突和髓鞘再生的影响。方法切断大鼠双侧坐骨神经，并予以端端吻合，分组分别联合给予不同时间的甲基强地松龙、CsA和FKS06（B组术后使用2d的甲基强地松龙20mg·kg^-1·d^-1；C组在B组的基础上，术后使用2周的FKS06。剂量为1mg·kg^-1·d^-1；D组在B组的基础上，术后使用4周的FKS06，剂量同C组；E组在B组的基础上。于术后使用2周的CsA，剂量为2mg·kg^-1·d^-1；F组在B组的基础上，于术后使用4周的CsA，剂量同E组），对照组（A组）不给药，于术后1、2、4周取材坐骨神经，分别进行苏木精-伊红染色、以及Nf和S100的免疫组织化学染色，并对染色结果进行分析、比较。结果从形态学观察，实验组较对照组神经吻合口远端的许旺细胞崩解不彻底，吻合口近端的神经轴突退变距离缩短，神经轴突生长速度更快，神经的再髓鞘化程度更高，早期即可见中央动脉形成。用药2周组与用药4周组在神经修复的组织学上无统计学意义（P〉0.05）。对NF和S100进行图像分析和统计学处理后，提示用药组神经生长速度显著快于对照组（A组），而联合用药组（C、E组）的神经生长速度在2周内比单纯使用甲基强地松龙组（B组）更快。联合用药组（C、E组）S100阳性染色的数量在2周内显著高于对照组（A组）。结论免疫抑制剂的使用可以对神经吻合口远端的许旺细胞和神经吻合口近端的神经细胞起到一定的保护作用，短期用药就可以取得与长时间用药相似的效果。

Objective To explore several immunosuppressants impact on the regeneration of axons and myelin sheath after rat sciatic nerve injury. Methods The sciatic nerves of rats were cut and sutured end - to - end. After operation, the rats were divided into 6 groups. Group A was served as control with no medicine administrated. Group B was administrated methylprednisolone with 20 mg·kg^-1·d^-1 for 2 days. Group C and D was administrated FK506 with 1 mg·kg^-1· d^-1 for 2 weeks and 4 weeks respectively plus the same dosage methylprednisolone as group B. Group E and F was administrated CsA with 2 mg·kg^-1·d^-1 for 2 weeks and 4 weeks respectively plus the same dosage methylprednisolone as group B. The sciatic nerves were sampled at 1, 2 and 4 weeks postoperatively. HE staining as well as immunohistochemistry staining of NF and S100 were performed. The staining results were compared and analyzed. Results Compared with the control group, in group B-F there were less myelin sheath collapsed in the distal stump, and shorter axon degeneration in the proximal stump. The speed of axon growth was also faster. And the meylination was quicker and better. The central arteries could be found in the early stage of nerve recovery. Among the experimental groups, there were no significant histological differences on the nerve regeneration for the rats with 2 - week medicine administration and those with 4 - weeks medicine administration. With the aid of image analysis and statistic procedure, it was found that the speed of axon growth in group B, C and E was much fater than that in group A, while the differences of axon growth speed between group B and group C and E were significant within 2 weeks after administration. Also the counts of S100 positive cells in group C and E were significantly higher than those in group A within 2 weeks after administration. Conclusion Immunosuppressants can protect the neurons as well as myelin sheath. Short administration of immunosuppressants can get the similar results as long - time administration.