抑制IKK2/NF-κB信号通路对骨癌痛大鼠模型的镇痛作用研究

Study of the analgesic effect of inhibiting IKK2/NF-κB signaling pathway on rat models with bone cancer pain

目的:研究抑制IKK2/NF-κB信号通路对骨癌痛大鼠模型的镇痛作用。方法:成年雄性SD大鼠被随机分为假手术组(S组)、骨癌痛模型组(BP组)和骨癌痛+BMS345541干预组(BB组),BP组和BB组在右侧胫骨中上段的髓腔注射Walker256乳腺癌细胞,S组注射生理盐水;建模后10d,BB组鞘内注射BMS345541,S组和BP组鞘内注射生理盐水。评估三组大鼠的机械痛阈值、脊髓中NF-κB、TNF-α、IL-6、GFAP、OX-42、CD-14、ITGAM的表达量以及血清中TNF-α、IL-6含量。结果:建模后、干预前(T1),BP组和BB组大鼠的MWT低于S组;干预后,BB组大鼠的MWT呈升高趋势且高于BP组;BB组大鼠脊髓组织中NF-κB的表达量低于BP组和S组,BP组和S组大鼠脊髓组织中NF-κB的表达量无差异;BP组大鼠血清中TNF-α、IL-6的含量高于S组,BB组大鼠血清中TNF-α、IL-6的含量低于BP组;BP组大鼠脊髓组织中TNF-α、IL-6、GFAP、OX-42、CD-14、ITGAM的含量高于S组,BB组大鼠脊髓组织中TNF-α、IL-6、GFAP、OX-42、CD-14、ITGAM的含量低于BP组。结论:抑制IKK2/NF-κB信号通路对骨癌痛大鼠模型具有镇痛作用,该信号通路作用的途径包括参与炎症因子的表达和胶质细胞的激活。

Objective： To study the analgesic effects of inhibiting IKK2/NF-κB signaling pathway on rat models＇with bone cancer pain. Methods： Adult male SD rats were randomly divided into sham group （S group）, bone cancer pain model group （BP group） and bone cancer pain ＋ BMS345541 intervention group （BB group）, BP group and BB group received injection of Walker256 breast cancer cells in pulp cavity of mid-upper part of right side of tibia, and S group received injection of normal saline; 10d after models were built, BB group received intrathecal injection of BMS345541, and S group and BP group received intrathecal injection of normal saline. MWT, expression levels of NF-κB, TNF-α, IL-6, GFAP, 0）（-42, CD-14 and ITGAM in spinal cord and contents of TNF-a and IL-6 in serum of three groups were assessed. Results： After models were es- tablished and before intervention （T1）, MWT of BP group and BB group was significantly lower than that of S group~ after in- tervention, MWT of BB group showed increasing trend and was higher than that of BP group; NF-κB expression level in spinal cord tissue of BB group was significantly lower than that of BP group and S group, and expression levels of NF-gB in spinal cord tissue of BP group and S group had no differenees; serum TNF-a and IL-6 contents of BP group were significantly higher than those of S group, and serum TNF-a and IL-6 contents of BB group were significantly lower than those of BP group; TNF- α, IL-6, GFAP, OX-42, CD-14 and ITGAM contents in spinal cord tissue of BP group were significantly higher than those of S group, and TNF-α, IL-6, GFAP, OX-42, CD-14 and ITGAM contents in spinal cord tissue of BB group were significantly lower than those of BP group. ConcLusion： Inhibiting IKK2/NF-κB signaling pathway has analgesic effect on rat models with bone cancer pain, and the ways of the signaling pathway include the participation in the expression of inflammatory factors and the activation of glial cells.