金天格胶囊通过抑制血管内皮细胞衰老并促进骨形成以缓解大鼠糖皮质激素性骨质疏松

doi:10.12122/j.issn.1673-4254.2026.04.14

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (4): 861-870.doi: 10.12122/j.issn.1673-4254.2026.04.14

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金天格胶囊通过抑制血管内皮细胞衰老并促进骨形成以缓解大鼠糖皮质激素性骨质疏松

邓子豪¹(), 王转¹(), 蒙森雄², 杨玉生¹, 杨运平¹(), 范刘奕¹(), 王磊¹()

^1.南方医科大学南方医院创伤骨科，广东广州 510515
^2.中山大学孙逸仙纪念医院心血管外科，广东广州 510000

收稿日期:2025-11-09 出版日期:2026-04-20 发布日期:2026-04-24
通讯作者: 杨运平,范刘奕,王磊 E-mail:2313588093@qq.com;1113014681@qq.com;yangyp2012@126.com;378280282@qq.com;conan213@smu.edu.cn
作者简介:邓子豪，在读硕士研究生，E-mail: 2313588093@qq.com
王转，在读硕士研究生，E-mail: 1113014681@qq.com
第一联系人：邓子豪、王转共同为第一作者
基金资助:
国家自然科学基金(82002352);金天格中青年科研培养基金（项目103）

Jintiange Capsule alleviates glucocorticoid-induced osteoporosis in rats by inhibiting vascular endothelial cell senescence and promoting bone formation

Zihao DENG¹(), Zhuan WANG¹(), Senxiong MENG², Yusheng YANG¹, Yunping YANG¹(), Liuyi FAN¹(), Lei WANG¹()

^1.Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
^2.Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510000, China

Received:2025-11-09 Online:2026-04-20 Published:2026-04-24
Contact: Yunping YANG, Liuyi FAN, Lei WANG E-mail:2313588093@qq.com;1113014681@qq.com;yangyp2012@126.com;378280282@qq.com;conan213@smu.edu.cn
Supported by:
National Natural Science Foundation of China(82002352)

摘要/Abstract

摘要：

目的验证细胞衰老在糖皮质激素性骨质疏松中的作用，探究金天格胶囊治疗糖皮质激素性骨质疏松的机制。方法复苏人脐静脉内皮细胞（HUVEC）和小鼠胚胎前成骨细胞（MC3T3），诱导生成破骨细胞，将上述细胞均分为对照组（CN组）、模型组（MPS组）和金天格处理组（MPS+JTG组），使用稀释后的生理盐水溶解甲基强的松龙和金天格胶囊，待细胞贴壁后分别使用相应的药物处理对应组别的细胞。通过蛋白印迹、SA-β-Gal染色、DCFH-DA法染色、划痕实验和RT-PCR检测HUVEC细胞的衰老通路、修复能力；通过免疫荧光染色、ALP染色、Alizarin Red S染色和RT-PCR检测MC3T3细胞成骨能力；通过TRAP染色检测破骨细胞分化程度。将30只3周龄SPF级雌性SD大鼠随机分为对照组（CN组）、模型组（MPS组）和金天格处理组（MPS+ JTG组），10只/组。建立糖皮质激素性骨质疏松模型并连续灌胃给药3个月。人道主义处死大鼠后取股骨及静脉血，进行micro-CT扫描、检测大鼠股骨骨体积分数变化情况，并检测大鼠血清骨代谢指标。结果网络药理学结果显示，虎骨有效成分与糖皮质激素性骨质疏松存在大量交集靶点，并与P53等细胞衰老相关靶点具有较强的结合力。在细胞水平，与模型组相比，在金天格处理后的HUVEC细胞模型中，P53、P21等衰老蛋白表达被抑制（P<0.01）、氧化应激减弱（P<0.01），而细胞迁移、成血管能力增强（P<0.05）。同样，金天格处理组的MC3T3细胞成骨和矿化能力也明显增强（P<0.001），并且抑制了破骨细胞的分化。在动物水平，经过14 d MPS腹腔注射的大鼠股骨骨量较对照组明显丢失，而金天格胶囊可以缓解骨量的丢失及血清骨代谢指标紊乱（P<0.05）。结论金天格胶囊可以通过抑制HUVEC细胞的衰老、增强MC3T3细胞的成骨能力并抑制破骨，促进骨髓内相关血管的迁移和生成，改善成骨能力和骨骼血供并促进成骨、抑制破骨，从而缓解糖皮质激素性骨质疏松。

关键词: 金天格胶囊, 糖皮质激素性骨质疏松, 细胞衰老, 血管再生, 成骨分化

Abstract:

Objective To investigate the role of cellular senescence in glucocorticoid-induced osteoporosis and explore the therapeutic mechanism of Jintiange (JTG) Capsule. Methods Cultured human umbilical vein endothelial cells (HUVECs) and mouse pre-osteoblasts (MC3T3) were treated with methylprednisolone (MPS) or MPS combined with JTG Capsule dissolved in saline. HUVEC senescence pathways and repair capacity were analyzed using Western blotting, SA-β-Gal staining, DCFH-DA assay, scratch wound healing, and RT-PCR. The osteogenic potential of MC3T3 cells was assessed using immunofluorescence staining, ALP staining, Alizarin Red S staining, and RT-PCR. Osteoclast differentiation was evaluated by TRAP staining. Thirty 3-week-old female SD rats were randomized into control, MPS, and MPS+JTG groups, and the rats in the latter two groups received daily intraperitoneal MPS injections and treated with gavage of saline or JTG Capsule suspension for 3 months. Femurs and venous blood were collected from the rats for micro-CT analysis of femoral bone volume fraction and detection of serum bone metabolism markers. Results Network pharmacology revealed that the active components of tiger bone had numerous intersection targets with glucocorticoid-induced osteoporosis with a strong binding affinity to cellular senescence-related targets such as P53. In MPS-treated HUVEC-derived osteoclasts, treatment with JTG Capsule significantly inhibited the expressions of P53 and P21, attenuated oxidative stress, and enhanced cell migration and angiogenic capacity. Similarly, JTG Capsule significantly enhanced osteogenic and mineralization capacities of MC3T3 cells and suppressed osteoclast differentiation. In the rat models, intraperitoneal MPS injection for 14 days resulted in significant bone loss in the femur, and JTG Capsule treatment obviously alleviated bone loss and ameliorated the disorder in serum bone metabolic markers. Conclusion JTG Capsule alleviates MPS-induced HUVEC senescence, enhances osteogenic capacity and suppresses osteoclastogenesis in MC3T3 cells, and promotes intraosseous angiogenesis to improve glucocorticoid-induced osteogenesis inrats.

Key words: Jintiange Capsule, glucocorticoid-induced osteoporosis, cell senescence, angiogenesis, osteogenic differentiation

邓子豪, 王转, 蒙森雄, 杨玉生, 杨运平, 范刘奕, 王磊. 金天格胶囊通过抑制血管内皮细胞衰老并促进骨形成以缓解大鼠糖皮质激素性骨质疏松[J]. 南方医科大学学报, 2026, 46(4): 861-870.

Zihao DENG, Zhuan WANG, Senxiong MENG, Yusheng YANG, Yunping YANG, Liuyi FAN, Lei WANG. Jintiange Capsule alleviates glucocorticoid-induced osteoporosis in rats by inhibiting vascular endothelial cell senescence and promoting bone formation[J]. Journal of Southern Medical University, 2026, 46(4): 861-870.

图/表 6

表1 MC3T3细胞成骨及HUVEC细胞衰老相关引物序列

Tab.1 Primer sequences for amplification of genes related with MC3T3 osteogenic differentiation and HUVEC cellular senescence

Gene	Primer sequences 5'-3'
P16-forward	ACCAGAGGCAGTAACCATGC
P16-reverse	GTGAAAAGGCAGAAGCGGTG
P21-forward	AGTCAGTTCCTTGTGGAGCC
P21-reverse	AGGAGAACACGGGATGAGGA
PLNB-forward	AGACTCTCCCAGCAACAAGC
PLNB-reverse	CTCTACTGCATCCTGAGGCG
ANG-forward	AGATTCTTCCTCCTGGGAGCC
ANG-reverse	CCAGCACGAAGACCAACAAC
BMP-2-forward	ACTCGAAATTCCCCGTGACC
BMP-2-reverse	CCACTTCCACCACGAATCCA
OCN-forward	ATGAGAGCCCTCACACTCCT
OCN-reverse	CTTGGACACAAAGGCTGCAC
RUNX2-forward	CGCCTCACAAACAACCACAG
RUNX2-reverse	TCACTGTGCTGAAGAGGCTG

图1 虎骨与GIO之间可能存在的潜在治疗靶向作用

Fig.1 Potential therapeutic targeting mechanism between HU and glucocorticoid-induced osteoporosis (GIO). A: Collection of GIO-related targets and screening of potential therapeutic targets. B: Construction and analysis of the active TB components-targets-GIO network. C: Protein-protein interaction (PPI) network of overlapping targets between TB active components and GIO treatment. D: Bar graph showing connectivity ranking of the core targets. E: Gene Ontology (GO) enrichment analysis. F: Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. G: Compound connectivity ranking of active ingredients in Hu Gu. H: Molecular docking results of glutamic acid (a key active component of TB) with P53 and IL6.

图2 金天格胶囊对血管内皮细胞氧化应激及衰老的作用

Fig.2 Effects of Jintiange (JTG) Capsule on oxidative stress and senescence in vascular endothelial cells. A, B: DCFH-DA staining for intracellular ROS detection (Original magnification: ×20). C, D: Senescence-associated β-galactosidase (SA-β-gal) staining for assessing the number of senescent cells in the 3 groups (×10). E-G: Western blotting for detecting P53 and P21 protein expression levels in the 3 groups. H, I: Quantitative PCR analysis of p16 and p21 mRNA expressions in the 3 groups. **P<0.01, ***P<0.001, ****P<0.0001.

图3 金天格胶囊对血管内皮细胞增殖及成血管作用的影响

Fig.3 Effects of JTG Capsule on proliferation and angiogenic activity of vascular endothelial cells. A, G: Scratch assay of HUVECs with different treatments for analyzing cell migration and proliferation. B, E: VEGF immunofluorescence staining in HUVECs in the 3 groups (×10). C, F: CD31 immunofluorescence staining in HUVECs with different treatments (×10). D, H: Tube formation assay of HUVECs cultured in conditioned media from each group for 24 h (×20). I, J: qPCR for detecting mRNA expression levels of angiogenesis-related markers Plexin-B2 (I) and ANG (J) in HUVECs. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

图4 金天格胶囊对成骨细胞及破骨细胞的影响

Fig.4 Effects of JTG Capsule on osteoblasts and osteoclasts. A, B: EdU labeling of MC3T3 cells with different treatment for analysis of cell proliferation (×10). C-E: Results of qPCR for detecting mRNA expressions of osteogenesis-related genes BMP-2 (C), OCN (D), and RUNX2 (E) in MC3T3 cells in the 3 groups. F: Osteogenic induction of MC3T3 cells in the 3 groups followed by alkaline phosphatase (ALP) staining and Alizarin Red S staining. G, H: Immunofluorescence staining of Osterix in MC3T3 cells with different treatments (×10). I: TRAP staining of the osteoclasts in the 3 treatment groups (×20). **P<0.01, ***P<0.001, ****P<0.0001.

图5 金天格胶囊在体外实验中对GIO患病大鼠的缓解作用

Fig.5 Therapeutic effects of JTG Capsule on glucocorticoid-induced osteoporosis (GIO) in rats. A: Micro-CT scanning of the femoral bones from rats in the 3 treatment groups. B-D: Quantitative analysis of micro-CT scans for measurement of bone volume (BV) (B), tissue volume (TV) (C), and BV/TV ratio (D). E, F: Serum levels of osteocalcin (OCN) and tartrate-resistant acid phosphatase 5b (TRAP-5b) (F) in GIO rats. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

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金天格胶囊通过抑制血管内皮细胞衰老并促进骨形成以缓解大鼠糖皮质激素性骨质疏松

Jintiange Capsule alleviates glucocorticoid-induced osteoporosis in rats by inhibiting vascular endothelial cell senescence and promoting bone formation

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