中药药理与临床2025，Vol.41Issue(6)：46-52,7.
壮骨镇痛胶囊调控破骨细胞活化治疗骨转移癌痛的作用机制研究
Mechanism of Action of Zhuanggu Analgesic Capsules in Treating Cancer-Induced Bone Pain via Regulating Osteoclast Activation
摘要
Abstract
Objective:Based on the Shenzhugu principle,this study investigated the mechanism of Zhuanggu Analgesic Capsules in treating cancer-induced bone pain via regulating osteoclast activation.Methods:Forty SPF female SD rats were randomly divided into a sham operation con-trol group and a modeling group.The right tibia of the rats was injected with MRMT-1 cells(breast cancer cells of rats)to establish a cancer-induced bone pain model.After successful modeling,the rats were randomly divided into a model control group(equal volume of sterile dis-tilled water),Zhuanggu Analgesic Capsule groups(0.567 g/kg and 1.134 g/kg),and zoledronic acid group(0.1 mg/kg).After four weeks of continuous administration,the general state and pain behavior of the rats were observed.Imaging was used to observe bone destruction in rats.Hematoxylin-eosin(HE)staining was used to observe pathological changes in bone tissue.Tartrate resistant acid phosphatase(TRAP)staining was used to detect the number of osteoclasts.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of osteo-clast activation marker type I collagen carboxyterminal peptide(CTX-I),TRCAP-5B,cathepsin K(CTSK),and matrix metalloproteinase-9(MMP-9).Western blot was used to detect the protein expressions of the key pathways for osteoclast activation,nuclear factor kappa B recep-tor activator(RANK)-RANKL-tumor necrosis factor receptor-associated factor-6(TRAF6),transcription factor active T cell nuclear factor 1(NFATC1),and C-FOS.Results:Compared with those in the sham operation control group,the mechanical foot contraction response thresh-old and thermal foot contraction latency in the model control group were reduced(P<0.05 or P<0.01),and significant bone destruction was observed,with decreased bone mineral content and bone density(P<0.01).A large number of tumor cells infiltrated the bone marrow cavity and invaded the cortical bone,causing abnormal disorder or even disappearance of the structure of the trabecular bone.The number of osteo-clasts significantly increased(P<0.01);the levels of CTX-I,TRACP-5B,CTSK,and MMP-9 were increased(P<0.01).The protein expres-sion of OPG in the bone was down-regulated,while the protein expressions of RANKL,RANK,and TRAF6 were increased(P<0.01).The protein expressions of NFATC1 and C-FOS were up-regulated(P<0.01).Compared with those in the model control group,the mechanical foot contraction response threshold and thermal foot contraction latency in each medication group were increased(P<0.05 or P<0.01).There were varying degrees of improvement in bone destruction,with an increase in bone mineral content and bone density(P<0.05).The area of tumor cell destruction was decreased,and the structure of the trabecular bone was normal.The number of osteoclasts was significantly de-creased(P<0.01).The serum levels of CTX-I,TRACP-5B,CTSK,and MMP-9 were decreased significantly(P<0.05).The protein expres-sion of OPG was up-regulated,while the protein expressions of RANKL,RANK,and TRAF6 were down-regulated(P<0.05 or P<0.01).The protein expressions of NFATC1 and C-FOS were down-regulated(P<0.05 or P<0.01).Conclusion:Zhuanggu Analgesic Capsules can sig-nificantly improve pain behavior and bone destruction in rats with cancer-induced bone pain,and its mechanism of action may be related to the inhibition of osteoclast activation.关键词
壮骨镇痛胶囊/骨转移癌痛/肾主骨/破骨细胞活化/核因子κB受体活化因子/RANKL-肿瘤坏死因子受体相关分子6/转录因子活性T细胞核因子1Key words
Zhuanggu Analgesic Capsule/Cancer-induced bone pain/Shenzhugu/Osteoclast activation/RANK/TRAF6/NFATC1引用本文复制引用
赖桂花,曹建雄,周君,王菲,聂多锐,文玲,马漪..壮骨镇痛胶囊调控破骨细胞活化治疗骨转移癌痛的作用机制研究[J].中药药理与临床,2025,41(6):46-52,7.基金项目
湖南省重点研发计划项目(编号:2018SK2127) （编号:2018SK2127）
湖南省中医药科研计划项目(编号:201946) （编号:201946）
2020年度湖南中医药大学中西医结合一流学科开放基金项目(编号:2020ZXYJH44) （编号:2020ZXYJH44）
中国博士后科学基金第75批面上(编号:1353). （编号:1353）
