免疫抑制剂对大鼠坐骨神经损伤修复后细胞因子表达的影响

目的初步探讨3种免疫抑制剂对大鼠坐骨神经损伤修复后细胞因子表达的影响。方法42只W istar大鼠制作动物模型,切断双侧坐骨神经,并予以端端吻合,分别联合给予不同组合的甲基强的松龙、环孢素A(C sA)和FK 506,A组(对照组,n=9)不给药,B组(n=9)术后使用2 d甲基强的松龙20 m g/(kg.d);C组(n=9)在B组的基础上,术后使用2周FK 506,剂量为1 m g/(kg.d);D组(n=3)在B组的基础上,术后使用4周FK 506,剂量同C组;E组(n=9)在B组的基础上,于术后使用2周C sA,剂量为2 m g/(kg.d);F组(n=3)在B组的基础上,于术后使用4周C sA,剂量同E组。于术后1、2和4周各组分别取双侧坐骨神经,进行白细胞介素1β(in terleuk in 1,βIL-1β)、肿瘤坏死因子α(tum or necros is factor,αTNF-α)、干扰素γ(in terferon,γIFN-γ)和巨噬细胞游走因子(m acrophage m igration inh ib itoryfactor,M IF)的免疫组织化学染色,并对染色结果进行分析、比较。结果A组修复后的坐骨神经IL-1β和IFN-γ的表达高峰出现于术后第1周,术后第2周表达量明显减少,至第4周就难以发现阳性染色;TNF-α和M IF的表达则只出现在第1周,且表达水平较低。各实验组IL-1β、TNF-α和IFN-γ的表达高峰均出现于术后第2周,且持续至第4周仍有表达,M IF的表达高峰出现在第1周,其表达也可持续至第4周。各实验组组间比较发现C~F组间细胞因子的表达无明显差异,B组的表达介于A组和其它实验组之间。结论免疫抑制剂的使用可以延缓周围神经损伤后IL-1β、TNFα-、IFN-γ和M IF表达的峰值,而且可以明显延长其表达时间。

EFFECTS OF IMMUNOSUPPRESSANTS ON CYTOKINE EXPRESSIONS AFTER REPAIR FOR NERVE INJURY IN A RAT MODEL

OBJECTIVE: To explore effects of several immunosuppressants on cytokine expressions after repair for a sciatic nerve injury in a rat model. METHODS: The sciatic nerves of 42 rats were cut and sutured end-to-end. After operation, the rats were divided into 6 groups. Group A (n = 9) was served as a control with no medicines given. Group B (n= 9) was given methylprednisolone 20 mg/(kg x d) for 2 days. Groups C(n= 9) and D(n = 3) were given FK506 1 mg/(kg - d) for 2 weeks and 4 weeks respectively, and were given the same doses of methylprednisolone as Group B. Groups E and F were given CsA 2 mg/(kg - d) for 2 weeks and 4 weeks respectively, and were given the same doses of methylprednisolone as Group B. The sciatic nerves were sampled at 1, 2 and 4 weeks postoperatively. And immuneohistochemistry stainings of interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interferon gamma(IFN-gamma) and macrophage migration inhibitory factor(MIF) were performed. The staining results were compared and analyzed. RESULTS: The expression peaks of IL-1beta and IFN-gamma were found at the 1st week postoperatively in Group A. Then, the expression decreased rapidly at the 2nd week and disappeared at the 4th week. As for TNF-a and MIF, they were only found to have a low expression until the 1st week in Group A. In groups C-F, the expression peaks of IL-1beta, TNF-alpha and IFN-gamma were found at the 2nd week, while the expression peak of MIF was still at the 1st week, and the expression of all the cytokines extended to the 4th week. The expressions of these cytokines in Group B were just between the expression levels of Group A and Groups C-F. CONCLUSION: Immunosuppressants can delay the expression peaks and significantly extend the expression time of IL-1beta, TNF-alpha, IFN-gamma and MIF after repair for a sciatic nerve injury in a rat model.