广东医学2025，Vol.46Issue(4)：519-524,6.DOI:10.13820/j.cnki.gdyx.20241992
地舒单抗对骨癌痛大鼠痛阈值、凝血功能及TAK1/JNK/c-Jun活性的影响
Effects of Denosumab on pain threshold,coagulation function and TAK1/JNK/c-Jun pathway activity in bone cancer pain rats
摘要
Abstract
Objective To study the effects of Denosumab on pain threshold,coagulation function and TAK1/JNK/c-Jun signaling pathway in bone cancer pain rats.Methods SD rats were randomly divided into four groups,sham operation group,model group,Denosumab group,and JNK inhibitor group.Except for the sham surgery group,rats in the other groups were injected with Walker 256 breast cancer cell suspension into the right tibia to establish a bone cancer pain model.After modeling,mechanical withdrawal threshold and thermal withdrawal latency were measured before and after drug administration.Conventional coagulation function indicators were detected,and X-ray images were used to assess bone destruction.Enzyme-linked immunosorbent assay(ELISA)was used to measure spinal cord-related cyto-kine levels,and Western blot was performed to detect the expression of proteins related to the TAK1/JNK/c-Jun signa-ling pathway.Results Compared with the sham surgery group,the model group showed a significant decrease in mechan-ical withdrawal threshold,thermal withdrawal latency,and coagulation function,with obvious bone destruction.The levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),interleukin-1 beta(IL-1 β),and monocyte che-moattractant protein(CCL2)were significantly increased,while the expression of p-TAK1,p-JNK,and p-c-Jun proteins in the spinal cord was significantly upregulated(P＜0.05).Compared with the model group,rats in the Deno-sumab and JNK inhibitor groups showed significant increases in mechanical withdrawal threshold and thermal withdrawal latency,improved coagulation function,and significant repair of bone destruction.The levels of TNF-α,IL-6,IL-1β,and CCL2 were significantly reduced,while the expression of p-TAK1,p-JNK,and p-c-Jun proteins in the spinal cord was significantly downregulated(P＜0.05).Conclusion Denosumab can alleviate bone cancer pain in rats,inhibit coagulation dysfunction,and reduce inflammation.Its mechanism may be related to the activation of the TAK1/JNK/c-Jun signaling pathway proteins.关键词
地舒单抗/骨癌痛/凝血功能/TAK1/JNK/c-Jun信号通路Key words
Denosumab/Bone cancer pain/Coagulation function/TAK1/JNK/c-Jun signaling pathway分类
医药卫生引用本文复制引用
段登科,白智龙,温振涛,王岩,孙邦建..地舒单抗对骨癌痛大鼠痛阈值、凝血功能及TAK1/JNK/c-Jun活性的影响[J].广东医学,2025,46(4):519-524,6.基金项目
河北省卫生健康委员会青年科技课题(20220492) （20220492）
邯郸市科学技术研究与发展计划(21422083062) （21422083062）
