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河北医学  2023, Vol. 29 Issue (11): 1767-1772    DOI: 10.3969/j.issn.1006-6233.2023.11.02
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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
徐成栋, 董晓俊, 李冬
湖北省武汉市中医医院骨伤科, 湖北 武汉 430014
Impact of Geniposide on Angiogenesis in Steroid-Induced Femoral Head Necrosis Rats by Regulating the HIF-1α/VEGF Signaling Pathway
XU Chengdong, DONG Xiaojun, LI Dong
Wuhan Traditional Chinese Medicine Hospital, Hubei Wuhan 430014, China
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摘要 目的: 探究栀子苷(GEN)调节缺氧诱导因子(HIF)-1α/血管内皮生长因子(VEGF)信号通路对激素性股骨头坏死大鼠血管生成的影响。方法: 随机选择18只大鼠记为空白对照组(NC组),其余大鼠构建糖皮质激素诱导的股骨头坏死(GIONFH)大鼠模型,将造模成功的大鼠随机平分为GIONFH组、GEN组(灌胃50mg/kg)、IDF-11774组(灌胃30mg/kg HIF-1α/VEGF信号通路抑制剂IDF-11774)、GEN+IDF-11774组(灌胃50mg/kg GEN以及30mg/kg IDF-11774),GEN和IDF-11774每天灌胃一次,持续四个月,每组均18只大鼠。GIONFH组、NC组仅灌胃等量生理盐水。对大鼠进行血管造影和股骨头显微CT扫描;ELISA法检测血清骨代谢指标水平;HE染色检测股骨组织病理变化;免疫组化染色检测股骨组织CD31、vWF表达;Western blot检测股骨组织HIF-1α/VEGF信号通路蛋白表达。结果: GIONFH组股骨头血管明显破坏,骨表面结构破坏,有大量空洞,股骨头软骨层变薄,骨排列稀疏无序,空腔增加,与NC组相比,GIONFH组血管体积、BV/TV、BALP、BGP含量、CD31、vWF阳性面积百分比、HIF-1α、VEGF蛋白水平均显著降低(P<0.05),CTX-I含量显著升高(P<0.05);与GIONFH组相比,GEN组对股骨头血管产生显著保护作用,股骨头表面光滑、结构完整,股骨头内部结构无明显异常,血管体积、BV/TV、BALP、BGP含量、CD31、vWF阳性面积百分比、HIF-1α、VEGF蛋白水平均显著升高(P<0.05),CTX-I含量显著降低(P<0.05),而IDF-11774组与GEN组以上指标结果相反;IDF-11774逆转了GEN对GIONFH大鼠血管生成的改善作用。结论: GEN可能通过激活HIF-1α/VEGF信号通路改善GIONFH大鼠血管生成。
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徐成栋
董晓俊
李冬
关键词 栀子苷HIF-1α/VEGF信号通路激素性股骨头坏死血管生成    
AbstractObjective: 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 wordsGeniposide    HIF-1α/VEGF signaling pathway    Glucocorticoid-induced osteonecrosis of the femoral head    Angiogenesis
    
基金资助:湖北省武汉市卫生健康委科研项目,(编号:WZ20D09)
引用本文:   
徐成栋, 董晓俊, 李冬. 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[J]. 河北医学, 2023, 29(11): 1767-1772.
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. HeBei Med, 2023, 29(11): 1767-1772.
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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.11.02     或     http://www.hbyxzzs.cn/CN/Y2023/V29/I11/1767
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