电针通过CXCR4-NLRP3通路参与调控小鼠骨癌痛的机制研究
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1.徐州医科大学江苏省麻醉学重点实验室;2.徐州医科大学附属医院疼痛科

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徐州重点研发计划(KC22235);江苏省研究生科研与实践创新计划项目(KYCX23_2962)


The mechanism of electroacupuncture in regulating bone cancer pain in mice through the CXCR4-NLRP3 pathway*
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1.Jiangsu Province Key Laboratory of Anesthesiology,Xuzhou Medical University;2.Department of Pain Medicine,The Affiliated Hospital of Xuzhou Medical University

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    摘要:

    目的:观察电针(electroacupuncture,EA)对骨癌痛(bone cancer pain,BCP)模型小鼠的镇痛效应,并研究电针对BCP小鼠脊髓内趋化受体因子4(CXCR4)和其下游炎症小体3(NLRP3)通路的影响,探索电针缓解骨癌痛的基础机制。方法:将C57BL/6小鼠随机分为对照组(Control)、模型组(BCP)、模型+电针组(BCP+EA)、模型+电针+溶剂组(BCP+EA+Veh)、模型+电针+激动剂组(BCP+EA+SDF-1),每组6只。使用Lewis肺癌细胞制备C57BL/6小鼠股骨癌痛动物模型。需要电针治疗的组别在造模后第8天到第14天在左侧足三里和昆仑穴电针,每天一次。观察各组小鼠左后足的机械刺激缩足反应阈值(mechanical withdraw threshold,MWT)热痛刺激的缩足潜伏期(paw withdraw latency,PWL)。采用免疫印迹检测小鼠L4-6脊髓内CXCR4、NLRP3、casepase-1、IL-1β的表达。结果:与对照组对比,BCP组小鼠从第7天开始MWT和PWL显著降低,CXCR4、NLRP3、casepase-1、IL-1β表达明显升高;与BCP组对比,BCP+EA组MWT和PWL明显升高,CXCR4、NLRP3、casepase-1、IL-1β表达明显降低;与BCP+EA+Veh组对比,BCP+EA+SDF-1组MWT和PWL明显降低,CXCR4、NLRP3、casepase-1、IL-1β表达明显升高。结论:电针治疗可以缓解BCP模型小鼠的痛觉过敏,这一作用可能和电针抑制CXCR4通路激活有关。

    Abstract:

    Objective: To observe the analgesic effect of electroacupuncture (EA) on bone cancer pain (BCP) model mice, and to study the effect of electroacupuncture on chemotactic receptor factor 4 (CXCR4) and its downstream inflammatory vesicle signaling pathway 3 (NLRP3) in the spinal cord of BCP mice, and to explore the basis of electroacupuncture to relieve bone cancer pain. mechanism. Methods: C57BL/6 mice were randomly divided into control (control), model (BCP), model + electroacupuncture (BCP+EA), model + electroacupuncture + solvent (BCP+EA+Veh), and model + electroacupuncture + agonist (BCP+EA+SDF-1) groups, with 6 mice in each group. Animal models of femoral cancer pain in C57BL/6 mice were established using Lewis lung cancer cells. Groups requiring electroacupuncture treatment received electroacupuncture at the Sanli and Kunlun points on the left foot on day 8 after modeling, once daily until day 14. Mechanical withdrawal threshold (MWT) for mechanical stimulation and paw withdrawal latency (PWL) for thermal pain stimulation were observed in the left hind paw of mice in each group. The expression of CXCR4, NLRP3, casepase-1, and IL-1β in the spinal cord of mice L4-6 was detected by immunoblotting. Results: Compared with the control group, mice in the BCP group showed a significant decrease in MWT and PWL and a significant increase in CXCR4, NLRP3, casepase-1, and IL-1β expression from day 7; compared with BCP group, BCP+EA group showed significant increase in MWT and PWL and significant decrease in CXCR4, NLRP3, casepase-1, and IL-1β expression; compared with BCP+EA+Veh group, MWT and PWL were significantly decreased and CXCR4, NLRP3, casepase-1, IL-1β expression was significantly increased in BCP+EA+SDF-1 group. Conclusion: Electroacupuncture treatment can alleviate nociceptive hypersensitivity in BCP model mice, and this effect may be related to the inhibition of CXCR4 pathway activation by electroacupuncture.

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  • 收稿日期:2024-11-12
  • 最后修改日期:2025-01-06
  • 录用日期:2025-09-18
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