白细胞介素-6在大鼠切割痛后脊髓中的表达和作用

目的探讨白细胞介素-6（IL-6）在大鼠切割痛后脊髓中的表达及作用。方法采用纵行切割大鼠后足作为疼痛模型,取切割后不同时间点（1、6、24、72h）及假手术组（未行手术组）大鼠腰髓节段采用实时定量PCR的方法观察IL-6mRNA的水平,并运用免疫组织化学与免疫荧光双标染色的方法,观察IL-6在腰段脊髓的表达及细胞定位;鞘内注射IL-6抗体中和内源性IL-6后,采用VonFrey尼龙纤维刺激后足以检测大鼠后足机械痛敏。结果大鼠后足切割1、6、24h后,其同侧腰段脊髓IL-6mRNA水平较假手术组分别上调1．43、1．74及1．46倍（t=3．315,P=0．016;t=5．121,P=0．0022;t=2．933,P=0．026）,免疫组织化学结果显示切割后6hIL-6在切割侧腰段脊髓后角表达明显增加（t=4．496,P〈0．05）,并且主要表达于神经元和内皮细胞中;鞘内给予IL-6抗体可明显增加大鼠后足切割后的缩足阈值。结论IL-6可能参与了大鼠后足切割后机械痛敏的过程,抑制IL-6的表达上调可能成为术后疼痛治疗的新靶点。

The role of interleukin-6 in incisional pain in the rats

Objective To investigate the expression of interleukin-6 （IL-6） and its role in inci- sional pain in the rat model. Methods Incisional pain rat model was established by a longitudinal incision in right plantar hind paw of isoflurane-anesthetized rats. Spinal cords were removed at various postoperative times （ 1, 6, 24, 72 h）. The gene expression of IL-6 in the spinal cord was determined by a Real-time PCR. Immunohistochemistry and double-labeling immunofluorescence were performed to determine the ex- pression of IL-6 after incision. Intrathecal injection of IL-6 antibodies was performed to modulate the spinal IL-6 after surgical incision, and the mechanical hypersensitivity was assessed by paw withdrawal thresholds from mechanical stimuli of von Frey filaments. Results After hind-paw incision, the IL-6 mRNA level was upregulated in the ipsilateral lumbar spinal cord. The immunoreactivity of IL-6 in spinal cord was increased after hind-paw incision at 6 hours after incision. The upregulated spinal IL-6 was mainly localized in the neurons and endothelial cells. Intrathecal injection of IL-6 antibodies dramatically inhibited the surgical in- cision that evoked pain hypersensitivity. Conclusions The present study showed that the upregulated IL-6 in the spinal cord contributed to the pain hypersensitivity after surgical incision, inhibiting the upregulated IL-6 in the spinal cord may be a possible new therapeutic target for the treatment of postoperative pain.