收稿日期: 2026-05-29
修回日期: 2026-06-16
录用日期: 2026-06-17
网络出版日期: 2026-08-13
基金资助
国家自然科学基金项目(82260858);国家自然科学基金项目(82460872);广西自然科学基金项目(2024GXNSFAA010243);广西高水平中医药重点学科建设试点项目(桂中医药科教发[2023]13号);广西中医药重点研究室建设项目(桂中医药科教发[2023]9号);广西研究生教育创新计划项目(YCBZ2025194)
The effect of Gujiansan on lipid metabolism disorder and osteogenesis impairment in rats with steroid-induced osteonecrosis of the femoral head
Received date: 2026-05-29
Revised date: 2026-06-16
Accepted date: 2026-06-17
Online published: 2026-08-13
目的 探讨骨坚散对激素性股骨头坏死模型大鼠骨、脂代谢的影响。 方法 将大鼠分为对照组、模型组和骨坚散低、中、高剂量组,每组10只。除对照组外,其余组均予脂多糖和糖皮质激素构建激素性股骨头坏死模型,骨坚散低、中、高剂量组分别予1.05、2.10、4.20 g/kg骨坚散每天灌胃。8周后检测血清低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)含量;RT-qPCR和Western blot分别检测股骨头组织中过氧化物酶体增殖物激活受体γ(PPARγ)、CCAAT增强子结合蛋白α(C/EBPα)、CCAAT增强子结合蛋白β(C/EBPβ)、Runt相关转录因子2(Runx2)、骨桥蛋白(OPN)、碱性磷酸酶(ALP)的mRNA和蛋白相对表达水平;Micro-CT观察大鼠股骨头骨质量的变化;苏木素-伊红(HE)染色观察股骨头组织病理形态变化;免疫组化(IHC)观察股骨头骨钙素(OCN)和Runx2蛋白表达。 结果 与模型组比较,骨坚散治疗后血清TC、TG及LDL-C含量减少(P < 0.05),而HDL-C含量增加(P < 0.05),PPARγ、C/EBPα、C/EBPβ mRNA和蛋白表达量降低(P < 0.05),Runx2、ALP、OPN的mRNA和蛋白表达量升高(P < 0.05),骨体积分数、骨小梁厚度、骨小梁数目、骨小梁连接密度及骨矿物质含量增加(P < 0.05),骨小梁分离度减少(P < 0.05),股骨头组织内空骨陷窝率降低(P < 0.05),OCN和Runx2蛋白表达水平升高(P < 0.05)。 结论 本研究显示,骨坚散低、中、高剂量组均具有调节骨脂代谢稳态的作用,且以骨坚散高剂量组作用最为显著;骨坚散可能通过PPARγ信号通路改善激素性股骨头坏死模型大鼠的脂代谢紊乱,促进成骨分化,恢复骨脂代谢平衡,进而促进骨坏死修复。
甘延池 , 周浩伟 , 马正安 , 吴亚超 , 韩杰 . 骨坚散对激素性股骨头坏死模型大鼠脂代谢紊乱和成骨障碍的影响[J]. 实用医学杂志, 2026 , 42(15) : 2798 -2807 . DOI: 10.3969/j.issn.1006-5725.2026.15.016
Objective To explore the effects of Gujiansan on bone and lipid metabolism in rat models of steroid-induced necrosis of the femoral head. Methods The rats were divided into the control group, the model group, and the low-dose, medium-dose, and high-dose groups of Gujiansan, with 10 rats in each group. Except for the control group, lipopolysaccharide and glucocorticoid were administered to the other groups to establish the steroid-induced necrosis of the femoral head model. The low-dose, medium-dose, and high-dose Gujiansan groups were respectively given 1.05, 2.10, and 4.20 g/kg of Gujiansan via gavage daily. Eight weeks later, the contents of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured. RT-qPCR and Western blot were employed to detect the relative mRNA and protein expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT enhancer binding protein α (C/EBPα), CCAAT enhancer binding protein β (C/EBPβ), Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and alkaline phosphatase (ALP) in femoral head tissues. Micro-CT was utilized to observe the alterations in the bone mass of the rat femoral head; Hematoxylin-eosin (HE) staining was used to observe the pathological morphological changes of the femoral head tissue. Immunohistochemistry (IHC) was applied to observe the protein expressions of osteocalcin (OCN) and Runx2 in the femoral head. Results Compared with the model group, after treatment with Gujiansan, the contents of serum TC, TG, and LDL-C decreased (P < 0.05), whereas the content of HDL-C increased (P < 0.05). Additionally, the mRNA and protein expression levels of peroxisome PPARγ, C/EBPα, and C/EBPβ decreased (P < 0.05), while those of Runx2, ALP, and OPN increased (P < 0.05). Moreover, the bone volume fraction, trabecular thickness, trabecular number, trabecular connection density, and bone mineral content increased (P < 0.05), the trabecular separation degree decreased (P < 0.05), the rate of empty bone pits in the femoral head tissue decreased (P < 0.05), and the expression levels of OCN and Runx2 proteins increased (P < 0.05). Conclusion This study shows that the low-dose, medium and high-dose groups of Gujiansan all have the effect of regulating the homeostasis of bone lipid metabolism, and the high-dose group of Gujiansan has the most significant effect; Gujiansan may improve lipid metabolism disorders in rats with steroid-induced necrosis of the femoral head via the PPARγ signaling pathway, promote osteogenic differentiation, restore the balance of bone-lipid metabolism, and consequently promote the repair of osteonecrosis.
| [1] | ZHANG J, CAO J, LIU Y, et al. Advances in the pathogenesis of steroid-associated osteonecrosis of the femoral head[J]. Biomolecules, 2024, 14(6): 667. doi:10.3390/biom14060667 . |
| [2] | ZHANG F, YAN Y, PENG W, et al. PARK7 promotes repair in early steroid-induced osteonecrosis of the femoral head by enhancing resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells via regulation of the Nrf2 signaling pathway[J]. Cell Death Dis, 2021, 12: 940. doi:10.1038/s41419-021-04226-1 . |
| [3] | KONARSKI W, POBO?Y T, KONARSKA K, et al. Osteonecrosis related to steroid and alcohol use-an update on pathogenesis[J]. Healthcare, 2023, 11(13): 1846. doi:10.3390/healthcare11131846 . |
| [4] | XIA C, XU H, et al. β-catenin inhibition disrupts the homeostasis of osteogenic/adipogenic differentiation leading to the development of glucocorticoid-induced osteonecrosis of the femoral head[J]. eLife, 2024, 12: RP92469. doi:10.7554/elife.92469 . |
| [5] | 李爱强, 赵宁, 张旭升, 等. 骨髓间充质干细胞来源细胞外囊泡治疗股骨头骨坏死的研究进展[J]. 实用医学杂志, 2025, 41(23): 3631-3637. doi:10.3969/j.issn.1006-5725.2025.23.001 . |
| [6] | ZHUANG J, WANG J, ZHANG B, et al. The prophylactic effects of naringin on steroid-induced early-stage osteonecrosis in rats: A preliminary study[J]. Cell Mol Biol (Noisy-le-grand), 2023, 69(5): 94-104. doi:10.14715/cmb/2023.69.5.16 . |
| [7] | ZHANG S, WANG H, MENG Q, et al. Recent advances in osteonecrosis of the femoral head: A focus on mesenchymal stem cells and adipocytes[J]. J Transl Med, 2025, 23(1): 592. doi:10.1186/s12967-025-06564-6 . |
| [8] | XU H, FANG L, ZENG Q, et al. Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH[J]. Food Funct, 2023, 14(2): 946-960. doi:10.1039/d2fo02337g . |
| [9] | ZUO B, WANG Z, LU H, et al. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head[J]. Open Med, 2025, 20: 20251145. doi:10.1515/med-2025-1145 . |
| [10] | WANG C, CEN C, SU H, et al. Integrated multi-omics analysis identifies lipid metabolism biomarkers in ONFH and reveals therapeutic potential of retinoic acid[J]. Sci Rep, 2025, 15: 30716. doi:10.1038/s41598-025-13703-y . |
| [11] | LIU N, ZHENG C, WANG Q, et al. Treatment of non-traumatic avascular necrosis of the femoral head (Review)[J]. Exp Ther Med, 2022, 23(5): 321. doi:10.3892/etm.2022.11250 . |
| [12] | SINGH M, SINGH B, SHARMA K, et al. A molecular troika of angiogenesis, coagulopathy and endothelial dysfunction in the pathology of avascular necrosis of femoral head: A comprehensive review[J]. Cells, 2023, 12(18): 2278. doi:10.3390/cells 12182278 . |
| [13] | HUA X, YU L, ZHU H, et al. Research progress of circRNAs in bone-related diseases[J]. Front Oncol, 2025, 15: 1481322. doi:10.3389/fonc.2025.1481322 . |
| [14] | 郭雪峰, 任艳玲, 于睿, 等. 基于 “久病入络” 理论探讨 “从虚而始, 因虚致瘀, 瘀痹骨络” 的激素性股骨头坏死核心病机观[J]. 中华中医药学刊, 2024, 42(6): 191-194. doi:10.13193/j.issn.1673-7717.2024.06.039 . |
| [15] | 杨阳, 吴健, 娄塞鹤, 等. 活血化瘀合滋补肝肾法对肾虚血瘀证早中期股骨头缺血性坏死患者的临床疗效[J]. 中成药, 2024, 46(3): 830-833. doi:10.3969/j.issn.1001-1528.2024. 03.019 . |
| [16] | 田照, 曾平, 刘金富, 等. 韦贵康运用骨坚散联合奇术手法治疗股骨头坏死经验[J]. 中医杂志, 2023, 64(9): 875-878. doi:10.13288/j.11-2166/r.2023.09.003 . |
| [17] | SUN H, ZHANG W, YANG N, et al. Activation of cannabinoid receptor 2 alleviates glucocorticoid-induced osteonecrosis of femoral head with osteogenesis and maintenance of blood supply[J]. Cell Death Dis, 2021, 12(11): 1035. doi:10.1038/s41419-021-04313-3 . |
| [18] | 陈奇. 中药药理研究方法学[M]. 3版. 北京: 人民卫生出版社, 2011: 1261-1262. |
| [19] | 雷宁波, 李盼盼, 邢涛, 等. 基于辨证论治理论剖析股骨头坏死的病因病机及其治疗进展[J]. 中医临床研究, 2025, 17(15): 75-81. doi:10.3969/j.issn.1674-7860.2025.15.017 . |
| [20] | 尚奇, 任辉, 沈耿杨, 等. 基于肾阴阳理论探讨自噬在激素性骨质疏松症中的作用[J]. 中华中医药杂志, 2018, 33(8): 3300-3303. |
| [21] | 区志坚, 李希文, 邱华耀, 等. 基于OPG/RANKL/RANK信号通路探究 “引血下行法” 调控激素性股骨头坏死骨代谢表达的影响[J]. 实用医学杂志, 2023, 39(23): 3058-3064. doi:10.3969/j.issn.1006-5725.2023.23.006 . |
| [22] | XIANG X N, HE H C, HE C Q. Advances in mechanism and management of bone homeostasis in osteonecrosis: A review article from basic to clinical applications[J]. Int J Surg, 2025, 111(1): 1101-1122. doi:10.1097/js9.0000000000002094 . |
| [23] | 丁志清, 郭小平, 潘珊珊, 等. 补肾活血法和痰瘀同治法治疗股骨头坏死的研究进展[J]. 中国民族民间医药, 2015, 24(4): 39-40. |
| [24] | 刘道兵, 王荣田, 陈卫衡. 从“痰瘀同病”论股骨头坏死的中医药治疗[J]. 中医杂志, 2013, 54(19): 1644-1646. |
| [25] | YU X, DOU S, LU L, et al. Relationship between lipid metabolism, coagulation and other blood indices and etiology and staging of non-traumatic femoral head necrosis: A multivariate logistic regression-based analysis[J]. J Orthop Surg Res, 2024, 19(1): 251. doi:10.1186/s13018-024-04715-x . |
| [26] | ZHONG D, XU G Z, WU J Z, et al. Circ-ITCH sponges miR-214 to promote the osteogenic differentiation in osteoporosis via upregulating YAP1[J]. Cell Death Dis, 2021, 12(4): 340. doi:10.1038/s41419-021-03586-y . |
| [27] | BURKHARDT L M, BUCHER C H, L?FFLER J, et al. The benefits of adipocyte metabolism in bone health and regeneration[J]. Front Cell Dev Biol, 2023, 11: 1104709. doi:10.3389/fcell. 2023.1104709 . |
| [28] | KIM J S, KIM J W, YEE J, et al. Interactive associations between PPARγ and PPARGC1A and bisphosphonate-related osteonecrosis of the jaw in patients with osteoporosis[J]. Pharmaceuticals, 2023, 16(7): 1035. doi:10.3390/ph16071035 . |
| [29] | LIU Y, HE T, LI Z, et al. TET2 is recruited by CREB to promote Cebpb, Cebpa, and Pparg transcription by facilitating hydroxymethylation during adipocyte differentiation[J]. iScience, 2023, 26(11): 108312. doi:10.1016/j.isci.2023.108312 . |
| [30] | YAN H, LI Q, LI M, et al. Ajuba functions as a co-activator of C/EBPβ to induce expression of PPARγ and C/EBPα during adipogenesis[J]. Mol Cell Endocrinol, 2022, 539: 111485. doi:10.1016/j.mce.2021.111485 . |
| [31] | SCHELLER E L, DOUCETTE C R, LEARMAN B S, et al. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues[J]. Nat Commun, 2015, 6: 7808. doi:10.1038/ncomms8808 . |
| [32] | GILLET C, DALLA VALLE A, GASPARD N, et al. Osteonecrosis of the femoral head: Lipotoxicity exacerbation in MSC and modifications of the bone marrow fluid[J]. Endocrinology, 2017, 158(3): 490-502. doi:10.1210/en.2016-1687 . |
| [33] | WANG J, ZHEN C, ZHANG G, et al. A 0.2 T–0.4 T static magnetic field improves the bone quality of mice subjected to hindlimb unloading and reloading through the dual regulation of BMSCs via iron metabolism[J]. Int J Mol Sci, 2024, 25(23): 13136. doi:10.3390/ijms252313136 . |
| [34] | GUO L, LI X, TANG Q Q. Transcriptional regulation of adipocyte differentiation: A central role for CCAAT/enhancer-binding protein (C/EBP) β[J]. J Biol Chem, 2015, 290(2): 755-761. doi:10.1074/jbc.R114.619957 . |
| [35] | WALEWSKA A, JANUCIK A, TYNECKA M, et al. Mesenchymal stem cells under epigenetic control–the role of epigenetic machinery in fate decision and functional properties[J]. Cell Death Dis, 2023, 14(11): 720. doi:10.1038/s41419-023-06239-4 . |
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