姜黄素抑制NF-κB信号通路缓解氧化应激对成骨分化的损害发挥抗骨质疏松作用  

Curcumin plays an anti-osteoporosis role by inhibitingNF-κB signaling pathway to reduce oxidative stress damage to osteogenesis

作　　者：胥甜甜[1] 田昊春 杨新民 罗栋华 王长根 漆启华[2] XU Tian-tian;TIAN Hao-chun;YANG Xin-min;LUO Dong-hua;WANG Chang-gen;QI Qi-hua(Pharmaceutical Dept,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Dept of Orthopedics,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Dept of Orthopedics,Ruizhou Hospital of Gaoan,Yichun Jiangxi 336000,China;Dept of Orthopedics,the People’s Hospital of Xunwu,Ganzhou Jiangxi 341000,China)

机构地区：[1]南昌大学第一附属医院药学部,江西南昌330006 [2]南昌大学第一附属医院骨科,江西南昌330006 [3]江西省高安市瑞州医院,江西宜春336000 [4]江西省赣州市寻乌县人民医院,江西赣州341000

出　　处：《中国药理学通报》2024年第1期46-54,共9页Chinese Pharmacological Bulletin

基　　金：江西省卫生健康委员会科技计划项目(No 20203182);国家自然科学基金资助项目(No 81960395)。

摘　　要：目的 探讨姜黄素抑制氧化应激对成骨分化损害的机制及以剂量依赖的方式发挥抗骨质疏松的作用。方法 采用细胞氧化应激模型,加入不同浓度的姜黄素,测定骨形成指标,并检测参与的潜在信号通路。同时,用姜黄素处理小鼠去卵巢(ovariectomized, OVX)骨质疏松动物模型来证实其抗骨质疏松的作用。结果 体外实验发现,低浓度姜黄素(1~10μmol·L^(-1))促进成骨细胞增殖,提高骨形成碱性磷酸酶(alkaline phosphatase, ALP)活性,逆转氧化应激导致的成骨钙沉积下降,降低了核因子kappa-B配体的受体激动剂(RANKL)和白介素-6 (IL-6)的表达。体内实验结果显示,姜黄素(5 mg·kg^(-1))给药后部分逆转了OVX小鼠血液中丙二醛(malondialdehyde, MDA)和谷胱甘肽(glutathione, GSH)活性的比例、降低高骨代谢、增加骨密度(bone density, BMD)、改善了骨小梁的微结构,但高浓度姜黄素无氧化应激保护作用。结论 姜黄素可以减轻氧化应激的骨形成损害,NF-κB信号通路是主要参与通路,姜黄素可能是预防骨质疏松症的理想药物。Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect.Methods Cellular oxidative stress models were used,different concentrations of curcumin were added to determinethebone formation markers,and the potential signaling pathways involvedwere detected.Meanwhile,the mouse model of osteoporosis(ovariectomized,OVX)was used to confirm its effect against osteoporosis.Results In vitro experiments found that low concentrations of curcumin(1-10μmol·L^(-1))promoted osteoblast proliferation,increasedthe activity of bone formation alkaline phosphatase(ALP),reversed the oxidative stress-induced decrease in osteoblast calcium deposition,and decreased the expression of the nuclear factors kappa-B ligands receptor agonists(RANKL)and interleukin-6(IL-6).In vivo results showed that curcumin administration partially reversed the ratio of malondialdehyde(MDA)and glutathione(GSH)activity,reduced high bone metabolism,increased bone density(BMD),and improved the microstructure of trabecular bone,but high concentration of curcumin showed noprotection from oxidative stress.Conclusions Curcumin can reduce the bone formation damage of oxidative stress,and the NF-κB signaling pathway is the main involved pathway,suggesting that curcumin may be an ideal drug to prevent osteoporosis.

关 键 词：姜黄素 核转录因子-ΚB 骨质疏松 骨形成 氧化应激 作用机制 

分 类 号：R-332[医药卫生] R282.71R336R349.1R681