CX3CR1参与NF-κB在脊髓水平调控大鼠癌痛的研究

Involvement of CX3CR1 in NF-κB regulated cancer pain in rat spinal cord

目的 研究鞘内注射核因子-κB（NF-κB）抑制剂二硫代氨基甲酸吡咯烷（pyrrolidine dithiocar-bamate,PDTC）对骨癌痛大鼠痛觉过敏、脊髓NF-κB和CX3CR1表达的影响.方法 雌性SD大鼠40只,随机分为5组（n=8）：对照组（naive组）、假手术组（sham组）、骨癌痛组（BCP组）、骨癌痛＋生理盐水组（BCP＋ saline组）、骨癌痛＋ PDTC 100 pmol·d-组（BCP＋PDTC组）.术后7～ 14天,BCP＋PDTC组将100pmol·d-1PDTC溶于10μl生理盐水鞘内注射;sham组、BCP＋ saline组给予等容积的生理盐水.分别测定0、1、3、5、7、9、11、14天的大鼠机械性痛觉过敏（PMWT）及自发性疼痛评分;Western blot法测定脊髓NF-κB和CX3CR1蛋白的表达水平.结果 与sham组比,术后第3天开始,BCP组大鼠PMWT减少,自发性疼痛评分增加（P＜0.05或P＜0.01）.与BCP＋ saline组比,BCP＋ PDTC组大鼠PMWT增加,自发性疼痛评分减少（P＜0.05或P＜0.01）.NF-κB和CX3CR1表达下调（P＜0.01）.结论 PDTC可以减轻骨癌痛大鼠的痛觉过敏,其机制可能与降低脊髓NF-κB和CX3CR1表达有关.

Objective To investigate the effect of intrathecal injection of pyrrolidine dithiocarbamate （PDTC, the inhibitor of NF - κB） on the pain hypersensitivity and the expression of NF - κB and CX3CR1 in the bone narrow of rats with bone cancer. Methods Forty female SD rats （ 150 - 180 g） were randomly divided into five groups （ n = 8 for each） ： a naive group, a sham group, a bone cancer pain （BCP） group, a BCP ＋ saline group, and a BCP ＋ PDTC group. Seven to fourteen days after operation, rats in the BCP ＋ PDTC group were intrathecally injected with 100 pmol/d PDTC in 10 μl normal saline, which the sham group and BCP ＋ saline group received the same volume of normal saline a- lone. Then, the paw mechanical withdrawal threshold （PMWT） and ambulatory pain score were measured on Days 0, 1, 3, 5, 7, 9, 11 and 14. The expressions of NF - κB and CX3CR1 in the spinal cord were determinect by western blotting. Results Compared with the sham group, the BCP group reported lower PMWTs but increased ambulatory pain scores （P 〈0.05 or P 〈 0.01 ）. However, increased PMWTs and reduced ambulatory pain scores were detected in the BCP ＋ PDTC group in contrast with the BCP ＋ saline group （ P 〈 0.05 or P 〈 0.01 ）. Western blot analysis showed that the expressions of NF - κB and CX3CR1 were remarkably enhanced in the spinal cord of the BCP ＋ PDTC group than those in the BCP ＋ saline group （ P 〈 0.01 ）. Conclusion PDTC can relieve the pain hypersensitivity of rats with bone cancer through inhibiting the expressions of NF - κB and CX3CR1 in the spinal cord.