中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (23): 6142-6149.doi: 10.12307/2026.353

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

复方补肾活血颗粒干预骨质疏松症模型小鼠:TRIB3/β-catenin轴的作用

王  岩1,吕  浩1,胡芷苜1,周  瑶1,刘  强1,杨玉祥1,衣海茹1,王久香2,江  渟2   

  1. 1安徽中医药大学第一临床医学院,安徽省合肥市   230031;2安徽中医药大学第一附属医院,安徽省合肥市   230031


  • 收稿日期:2025-05-06 接受日期:2025-08-22 出版日期:2026-08-18 发布日期:2026-01-06
  • 通讯作者: 江渟,博士,主任医师,博士生导师,安徽中医药大学第一附属医院,安徽省合肥市 230031 并列通讯作者:王久香,博士,副研究员,硕士生导师,安徽中医药大学第一附属医院,安徽省合肥市 230031
  • 作者简介:王岩,男,2002年生,河北省永清县人,汉族,安徽中医药大学在读硕士,主要从事中医药防治骨伤科疾病的研究。 并列第一作者:吕浩,男,1997年生,安徽省来安县人,汉族,安徽中医药大学在读博士,主要从事中医药防治骨伤科疾病的研究。
  • 基金资助:
    安徽省自然科学基金项目(面上项目)(2308085MH294),项目负责人:江渟;安徽省重点研究与计划开发项目(202104j07020010) ,项目负责人:江渟;安徽省教育厅自然科学研究(重点项目)(2022AH050510),项目负责人:江渟;安徽省自然科学基金项目(面上项目)(2408085MH226),项目负责人:王久香

Intervention with Compound Kidney-Invigorating Granules in a mouse model of osteoporosis: role of the TRIB3/beta-catenin axis

Wang Yan1, Lyu Hao1, Hu Zhimu1, Zhou Yao1, Liu Qiang1, Yang Yuxiang1, Yi Hairu1, Wang Jiuxiang2, Jiang Ting2   

  1. 1The First Clinical Medical College of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China; 2The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
  • Received:2025-05-06 Accepted:2025-08-22 Online:2026-08-18 Published:2026-01-06
  • Contact: Wang Jiuxiang, MD, Associate researcher, Master’s supervisor, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
  • About author:Wang Yan, MS candidate, the First Clinical Medical College of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China Lyu Hao, MD candidate, the First Clinical Medical College of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China Wang Yan and Lyu Hao contributed equally to this work. Corresponding author: Jiang Ting, MD, Chief physician, Doctoral supervisor, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
  • Supported by:
    the Natural Science Foundation of Anhui Province (General Program), No. 2308085MH294 (to JT); Anhui Provincial Key Research and Development Project, No. 202104j07020010 (to JT); the Scientific Research Foundation of the Education Department of Anhui Province, No. 2022AH050510 (to JT); the Natural Science Foundation of Anhui Province (General Program), No. 2408085MH226 (to WJX)

摘要:



文题释义:
TRIB3/β-catenin轴:β-catenin在成骨细胞发育中起着至关重要的作用,TRIB3 是调控干细胞成骨-成脂分化的关键分子。体外研究发现TRIB3可与β-catenin结合,促进β-catenin进入细胞核,激活Wnt/β-catenin信号通路,控制骨髓间充质干细胞的分化选择,最终使骨髓间充质干细胞倾向成骨细胞分化。研究表明TRIB3/β-catenin轴在成骨分化过程中起重要作用。
骨小梁:是构成松质骨的网状结构单位,它们像桥梁一样,纵横交错、互相连接,构成一个具有弹性和支撑性的骨架网。

背景:前期研究发现,敲低β-catenin可抑制人骨髓间充质干细胞成骨分化能力,降低TRIB3的表达,复方补肾活血颗粒含药血清干预后可以促进人的骨髓间充质干细胞中β-catenin与TRIB3的表达,诱导人骨髓间充质干细胞向成骨分化。
目的:基于TRIB3/β-catenin轴进一步探讨复方补肾活血颗粒对骨质疏松症模型小鼠的作用机制。
方法:将8周龄雌性C57BL/6小鼠随机分为空白对照组、假手术组、模型组及复方补肾活血颗粒低、中、高剂量组和阳性药组。除空白对照组和假手术组小鼠外,其余各组小鼠切除双侧卵巢建立骨质疏松症小鼠模型。造模1周后,复方补肾活血颗粒低、中、高剂量组小鼠分别给予7.05,14.1,28.2 g/kg复方补肾活血颗粒灌胃,空白对照组、假手术组和模型组小鼠给予等体积的生理盐水灌胃,每日1次;阳性对照组小鼠给予1.53 mg/kg阿仑膦酸钠灌胃每周1次。灌胃12周后Micro-CT检测小鼠的股骨骨微结构变化,苏木精-伊红染色、Masson 染色检测股骨病理变化,Western Blot检测骨组织中TRIB3、β-catenin及碱性磷酸酶、骨桥蛋白表达水平。
结果与结论:与空白对照组及假手术组比较,模型组骨组织骨小梁排列稀疏,空骨陷窝数较对照组明显增多;TRIB3、β-catenin、碱性磷酸酶、骨桥蛋白的蛋白表达水平均显著降低(P < 0.05)。与模型组相比,复方补肾活血颗粒中、高剂量组骨小梁形态较为完整,排列较为规则,TRIB3、β-catenin、碱性磷酸酶、骨桥蛋白的蛋白表达水平均显著上调(P < 0.05)。结果说明,复方补肾活血颗粒对骨质疏松模型小鼠起到治疗作用,提示该方可能是通过TRIB3/β-catenin轴产生的作用。
https://orcid.org/0009-0007-2756-9087 (王岩);https://orcid.org/0000-0001-6758-8492 (吕浩)


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 骨质疏松症, 复方补肾活血颗粒, TRIB3, β-catenin, 中药复方, 模型小鼠, 碱性磷酸酶, 骨组织

Abstract: BACKGROUND: Previous studies have shown that knockdown of β-catenin can inhibit the osteogenic differentiation of human bone marrow mesenchymal stem cells and reduce the expression of TRIB3. Serum containing Compound Kidney-Invigorating Granules can promote the expression of β-catenin and TRIB3 in human bone marrow mesenchymal stem cells, and induce human bone marrow mesenchymal stem cells to differentiate into osteogenic cells.
OBJECTIVE: To further explore the mechanism of Compound Kidney-Invigorating Granules in a mouse model of osteoporosis based on the TRIB3/β-catenin axis. 
METHODS: 8-week-old female C57BL/6 mice were randomly divided into the following experimental groups: blank control group, sham surgery group, model group, low-, medium-, and high-dose groups of Compound Kidney-Invigorating Granules, and a positive drug group. Except for the blank control and sham surgery groups, the bilateral ovaries of mice were removed to construct osteoporosis models. One week after model preparation, mice were given 7.05, 14.1 and 28.2 g/kg Compound Kidney-Invigorating Granules in the low-, medium- and high-dose Compound Kidney-Invigorating Granule groups, respectively. Mice in the positive drug group were given 1.53 mg/kg alendronate sodium by intragastric administration, and those in the blank control group and sham surgery group were given an equal volume of normal saline, once a day. After 12 weeks of intragastric administration, the bone microstructures of mice in different groups were observed by Micro-CT. The pathological changes in the femur were detected by hematoxylin-eosin staining and Masson staining; and expressions of TRIB3, β-catenin and osteogenic proteins (alkaline phosphatase and osteopontin) in the femur were detected by western blot assay.  
RESULTS AND CONCLUSION: Compared with the blank control group and sham surgery group, the bone trabecular arrangement in the model group was sparse, and the number of empty bone lacunae was significantly increased. The expression levels of TRIB3, β-catenin, alkaline phosphatase and osteopontin were significantly decreased (P < 0.05). Compared with the model group, bone trabeculae in the medium- and high-dose groups of Compound Kidney-Invigorating Granules showed more intact morphology and regular arrangement. The protein expression levels of TRIB3, β-catenin, alkaline phosphatase and osteopontin were significantly up-regulated (P < 0.05). Therefore, these findings indicate that Compound Kidney-Invigorating Granules have a therapeutic effect on osteoporosis model mice, and its mechanism may be generated through the TRIB3/β-catenin axis. 


Key words: osteoporosis, Compound Kidney-Invigorating Granule, TRIB3, β-catenin, Chinese herbal compound, mouse model, alkaline phosphatase, bone tissue

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