巨噬细胞游走抑制因子在复杂区域疼痛综合征1型胫骨骨折大鼠模型中的表达及作用

Expression and function of macrophage migration inhibitory factor in a rat tibia fracture model of complex regional pain syndrome type Ⅰ

目的探讨巨噬细胞游走抑制因子(MIF)在复杂区域疼痛综合征1型(CRPS1)的表达及MIF靶向阻断对CRPS1大鼠疼痛行为的影响。方法健康成年雄性SD大鼠50只,随机分为正常组、假手术组、模型组、治疗对照组及MIF抑制剂(ISO-1)治疗组。后3组均进行CRPS1远端胫骨骨折造模;ISO-1治疗组在骨折2周后开始将ISO-1溶解于10μl5%DMSO后行皮下注射,1mg/(kg.d),连续14d;治疗对照组同期皮下注射10μl 5%DMSO作为对照。测定各组大鼠治疗前后下肢肿胀程度及痛觉阈值并进行比较;采用ELISA、蛋白质印迹法测定各组大鼠血清、脑脊液、皮肤、坐骨神经和脊髓中MIF蛋白的表达并进行比较。结果模型组大鼠后足明显肿胀,疼痛阈值明显下降,与基线值及对照组比较,差异有统计学意义(P<0.01)。MIF抑制剂ISO-1治疗组的下肢肿胀及痛觉阈值均有改善,与模型组相比较,差异有统计学意义(P<0.05)。模型组、治疗对照组及MIF抑制剂(ISO-1)治疗组的MIF在血清、脑脊液、皮肤、坐骨神经和脊髓的表达均高于正常对照组,差异有统计学意义(P<0.05或P<0.01)。结论 MIF是CRPS1的关键性炎症因子,抗MIF可能成为其新的靶向治疗手段。

Objective To investigate the expression of macrophage migration inhibitory factor （MIF） in complex regional pain syndrome Ⅰ （CRPS Ⅰ ） rat model and the possible efficacy of MIF blockage in treatment of CRPSⅠ . Methods Fifty healthy male SD rats were randomly divided into the following 5 groups： control, sham, model, DMSO control, and ISO-1 （inhibitor of MIF） treatment. CRPS1 models were created in the last 3 groups; rats in the ISO-1 treatment group were subcutaneously treated with ISO-1 dissolved in 10 μ1 5% DMSO at 1 mg/（kg · d） for 14 d. DMSO control group was only given 10μ 50/00 DMSO. The pain threshold and thickness of the hindpaws were measured before and after treatment and were compared. The levels of MIF protein were examined in the serum, skin, spinal cord, sciatic nerve, and cerebrospinal fluid using ELISA and Western blotting analysis. Results Rats in the model group had noticeable hindpaw edema and significantly decreased pain threshold compared with the baselihe and that of the control group（P〈0.01） . The hindpaw edema and pain threshold were significantly improved in ISO-1 treatment group compared with those in the model group（P〈0.05）. MIF levels in the serum, skin, spinal cord, cerebrospinal fluid and sciatic nerve were higher in the model, DMSO control, and ISO-1 groups compared with those in the control group （P〈0.05 or P〈0.01）. Conclusion MIF is a key inflammatory factor of CRPS I , and anti-MIF treatment might be a new therapy for human CRPS Ⅰ.