栀子苷调节HIF-1α/VEGF信号通路对激素性股骨头坏死大鼠的血管生成的影响

doi:10.3969/j.issn.1006-6233.2023.11.02

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Abstract Objective: To investigate the impact of geniposide (GEN) on angiogenesis in rats with steroid-induced femoral head necrosis via the regulation of hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. Methods: 18 rats were randomly marked a blank control group (NC group),while the remaining rats were used to create a rat model of glucocorticoid-induced osteonecrosis of the femoral head (GIONFH).The rats in the GIONFH group were further randomized into the following groups:GIONFH group,GEN group (gavaged with 50mg/kg of GEN),IDF 11774 group (gavaged with 30mg/kg of HIF-1α/VEGF signaling pathway inhibitor IDF 11774),and GEN+IDF 11774 group (gavaged with 50mg/kg GEN and 30mg/kg IDF 11774).GEN and IDF 11774 were administered by gavage daily for four months,with 18 rats in each group.The GIONFH and NC groups were given an equal volume of physiological saline by gavage.Angiography and micro CT scanning were performed on the femoral heads.Serum bone metabolism indicators were measured using the ELISA method.Histological changes in the femoral tissue were assessed through HE staining.Immunohistochemical staining was conducted to evaluate the expression of CD31 and vWF in the femoral tissue.Western blot analysis was performed to examine the protein expression of the HIF-1α/VEGF signaling pathway in femoral tissue. Results: The GIONFH group exhibited severe damage to femoral head blood vessels,disrupted bone surface structures,extensive cavities,thinning of the femoral head cartilage layer,disordered bone arrangement,and increased cavities.Compared to the NC group,the GIONFH group showed significantly reduced vascular volume,BV/TV,BALP,BGP content,CD31,vWF positive area percentage,HIF-1α,and VEGF protein levels (P<0.05),while CTX-I content significantly increased (P<0.05).In contrast,the GEN group provided substantial protection to the femoral head blood vessels,resulting in smoother femoral head surfaces with intact structures and no observable internal abnormalities.The vascular volume,BV/TV,BALP,BGP content,CD31,vWF positive area percentage,HIF-1α,and VEGF protein levels were significantly elevated (P<0.05),and the CTX-I content markedly decreased (P<0.05) compared to the GIONFH group.These effects were reversed in the IDF 11774 group. Conclusion: Geniposide (GEN) may improve angiogenesis in GIONFH rats by activating the HIF-1α/VEGF signaling pathway.

Key words： Geniposide HIF-1α/VEGF signaling pathway Glucocorticoid-induced osteonecrosis of the femoral head Angiogenesis

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	XU Chengdong
	DONG Xiaojun
	LI Dong

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XU Chengdong,DONG Xiaojun,LI Dong. Impact of Geniposide on Angiogenesis in Steroid-Induced Femoral Head Necrosis Rats by Regulating the HIF-1α/VEGF Signaling Pathway[J]. HeBei Med, 2023, 29(11): 1767-1772.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.11.02 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I11/1767

[1] Xu J,Gong H,Lu S,et al.Animal models of steroid-induced osteonecrosis of the femoral head-a comprehensive research review up to 2018[J].Int Orthop,2018,42(7):1729-1737.
[2] Xiao Y,Ren Q,Zheng Y,et al.Geniposide ameliorated dexamethasone-induced endoplasmic reticulum stress and mitochondrial apoptosis in osteoblasts[J].Ethnopharmacol,2022,291(1):115154-115168.
[3] Li J,Fan L,Yu Z,et al.The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads[J].Exp Biol Med (Maywood),2015,240(2):273-280.
[4] Zhang C,Wang N,Tan HY,et al.Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma[J].Br Pharmacol,2020,177(14):3240-3257.
[5] Huang J,Ye Y,Xiao Y,et al.Geniposide ameliorates glucocorticoid-induced osteoblast apoptosis by activating autophagy[J].Biomed Pharmacother,2022,155(5):113829-113843
[6] Tian L,Baek SH,Jang J,et al.Anti-tumor effect of IDF-11774,an inhibitor of hypoxia-inducible factor-1,on melanoma[J].Biomol Ther (Seoul),2022,30(5):465-472.
[7] Zhao D,Zhang F,Wang B,et al.Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version)[J].Orthop Translat,2020,21(1):100-110.
[8] Chen L,Huang X,Li X,et al.Geniposide promotes the proliferation and differentiation of MC3T3-E1 and ATDC5 cells by regulation of microRNA-214[J].Int Immunopharmacol,2020,80(1):106121-106129.
[9] Zheng Y,Xiao Y,Zhang D,et al.Geniposide ameliorated dexamethasone-induced cholesterol accumulation in osteoblasts by mediating the GLP-1R/ABCA1 axis[J].Cells,2021,10(12):3424-3438.
[10] Tian L,Baek SH,Jang J,et al.Imbalanced bone turnover markers and low bone mineral density in patients with osteonecrosis of the femoral head[J].Int Orthop,2018,42(7):1545-1549.
[11] Chang CJ,Jou IM,Wu TT,et al.Cigarette smoke inhalation impairs angiogenesis in early bone healing processes and delays fracture union[J].Bone Joint Res,2020,9(3):99-107.
[12] Peng Y,Wu S,Li Y,et al.Type H blood vessels in bone modeling and remodeling[J].Theranostics,2020,10(1):426-436.