姜黄素通过Wnt/β-catenin信号通路调控成骨分化治疗骨质疏松的潜在机制  

Potential Mechanism of Curcumin in Regulating Osteogenic Differentiation to Treat Osteoporosis through Wnt/β-catenin Signaling Pathway

作　　者：赵灿斌 秦英 孙宏章 闫小龙[4] 李晓阳 陈东峰 管东辉[5] 邵将 ZHAO Can-bin;QIN Ying;SUN Hong-zhang;YAN Xiao-long;LI Xiao-yang;CHEN Dong-feng;GUAN Dong-hui;SHAO Jiang(First Clinical Faculty of Guangxi University of Chinese Medicine,Nanning Guangxi 530200;Orthopedics Department,Jinan Changqing District Hospital of Traditional Chinese Medicine,Jinan Shandong 250300;First Clinical Medical School,Shandong University of Traditional Chinese Medicine,Jinan Shandong 250014;Emergency and Critical Care Medicine Center,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan Shandong 250014;Orthopedics Department,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan Shandong 250014)

机构地区：[1]广西中医药大学第一临床医学院,广西南宁530200 [2]济南市长清区中医医院骨科,山东济南250300 [3]山东中医药大学第一临床医学院,山东济南250014 [4]山东中医药大学附属医院急诊重症医学中心,山东济南250014 [5]山东中医药大学附属医院骨科,山东济南250014

出　　处：《世界中西医结合杂志》2025年第3期514-523,共10页World Journal of Integrated Traditional and Western Medicine

基　　金：山东省自然科学基金(ZR2022MH147);山东省中医药科技青年项目(2020Q016)。

摘　　要：目的研究姜黄素(Curcumin)促进成骨分化、治疗去势卵巢SD大鼠骨质疏松症的作用机制及对其Wnt/β-catenin信号通路的调控作用。方法通过网络药理学方法获取姜黄素调控成骨分化的靶点基因,构建蛋白质作用网络(Protein-protein interaction,PPI),并进行GO、KEGG富集分析及分子对接处理。通过双卵巢摘除构建SD大鼠骨质疏松模型,将48只SPF级雌性SD大鼠按随机数字表法分为对照组、模型组、姜黄素低剂量组[10 mg/(kg·d)]、姜黄素高剂量组[20 mg/(kg·d)],每组各12只。对照组生理盐水灌胃,其他各组均灌胃给药,1次/d,8周,取脱钙股骨组织标本,HE染色观察各组骨组织形态,茜素红染色观察各组钙盐沉积情况,Micro-CT扫描各组股骨近段组织,RT-qPCR检测Wnt/β-catenin信号通路及成骨相关基因的mRNA表达情况,Western Blot及免疫组化检测Wnt/β-catenin信号通路及成骨相关基因的蛋白表达情况。结果筛选出姜黄素调控成骨分化的靶点基因92个,主要涉及细胞迁移正向调控,蛋白质磷酸化等生物过程。其中,有3个靶点基因作用于Wnt/β-catenin信号通路,且均可以与姜黄素良好对接。此外,姜黄素可改善骨质疏松大鼠骨微结构,提高单位体积内骨小梁数量,促进骨组织内钙盐沉积。姜黄素可提高骨质疏松大鼠骨组织中Wnt/β-catenin信号通路及成骨相关基因的mRNA及蛋白的表达(P<0.05)。结论姜黄素可通过调控Wnt/β-catenin信号通路促进成骨分化,防治骨质疏松的发生发展。Objective To analyze the mechanism of curcumin in promoting osteogenic differentiation to cure osteoporosis in ovariectomized SD rats,as well as curcumin′s regulation in Wnt/β-catenin signaling.Methods Network pharmacology methods were employed to obtain target genes regulated by curcumin for osteogenic differentiation.Then,a network of protein interactions(PPI)was built while molecular docking,as well as GO and KEGG enrichment analysis,were carried out.Bilateral ovariectomy was conducted in SD rats to establish a rat model of osteoporosis.48 female SD rats with SPF levels were divided into a control group,a model group,a low-dose curcumin group[10 mg/(kg·d)],and a high-dose curcumin group[20 mg/(kg·d)]using random number table method,with 12 rats in each group.All groups received intragastric administration once daily for 8 consecutive weeks.Saline was given to the control group while curcumin was given to the rest of the groups.Afterward,decalcified femur tissue samples were obtained.On this basis,HE staining was used to observe the bone tissue morphology in each group,Alizarin Red staining was used to observe calcareous deposit,Micro-CT was used to scan proximal femoral tissues,RT-qPCR was used to detect the mRNA expression of Wnt/β-catenin signaling pathway and osteogenic-related genes,and Western blot as well as immunohistochemistry were used to detect the protein expression of Wnt/β-catenin signaling and osteogenic-related genes.Result 92 target genes regulated by curcumin for osteogenic differentiation were screened,primarily involving biological processes including positive regulation of cell migration and protein phosphorylation.Among the genes screened,three of those acting on the Wnt/β-catenin signaling pathway could all dock well with curcumin.In addition,curcumin could improve the bone microstructure of osteoporosis rats,increase the number of bone trabeculae per unit volume,and promote calcareous deposit in bone tissue.Curcumin could increase the mRNA and protein expression of Wnt/β-catenin

关 键 词：姜黄素 成骨分化 骨质疏松 网络药理学 WNT/Β-CATENIN信号通路 

分 类 号：R285.6[医药卫生—中药学]