[1]韦志坤,杨芳,邵菲,等.山奈酚调节信号通路促进大鼠血管生成和骨折愈合[J].中国中医骨伤科杂志,2025,33(03):18-23.[doi:1005-0205(2025)03-0018-06]
　WEI Zhikun,YANG Fang,SHAO Fei,et al.Kaempferol Promotes Angiogenesis and Fracture Healing in Rats by Regulating Notch Signal Pathway[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2025,33(03):18-23.[doi:1005-0205(2025)03-0018-06]
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山奈酚调节信号通路促进大鼠血管生成和骨折愈合()
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《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第33卷
期数:
2025年03期
页码:
18-23
栏目:
实验研究
出版日期:
2025-03-15

文章信息/Info

Title:
Kaempferol Promotes Angiogenesis and Fracture Healing in Rats by Regulating Notch Signal Pathway
文章编号:
10.20085/j.cnki.issn1005-0205.250304
作者:
韦志坤1;  杨芳2;  邵菲1;  杨金杰1;  王旭东1;  李树彬1;  刘志翔1;  刘杰1;  任少海1
1邯郸市第一医院(河北 邯郸,056000)
2邯郸市中心医院
Author(s):
WEI Zhikun1;  YANG Fang2;  SHAO Fei1;  YANG Jinjie1;  WANG Xudong1;  LI Shubin1;  LIU Zhixiang1;  LIU Jie1;  REN Shaohai1
1Handan First Hospital,Handan 056000,Hebei China; 2Handan Central Hospital,Handan 056000,Hebei China.
关键词:
山奈酚;  信号通路;  骨折愈合;  血管生成;  骨形成
Keywords:
kaempferol;  Notch signal pathway;  fracture healing;  angiogenesis;  bone formation
分类号:
R-33
DOI:
1005-0205(2025)03-0018-06
文献标志码:
A
摘要:
目的:探究山奈酚通过调节Notch信号通路促进大鼠骨折愈合和血管生成。方法:随机选择18只大鼠作为假手术组,其余大鼠构建骨折大鼠模型,将造模成功的骨折大鼠随机平分为模型组、山奈酚组(腹腔注射100 mg/(kg?d)山奈酚)、抑制剂组(腹腔注射5 mg/(kg?d)Notch信号通路抑制剂DAPT)、山奈酚+抑制剂组(腹腔注射100 mg/(kg?d)山奈酚和5 mg/(kg?d)DAPT),连续治疗8周,每组均18只。微型计算机断层扫描分析骨折愈合情况; ELISA法检测骨代谢指标; 免疫荧光染色检测CD31表达; Western Blot法检测骨形成标志物(BMP2、SOX9)、血管生成标志物(VEGF和MMP9)以及Notch信号通路蛋白表达。结果:X射线图像表明,模型组骨折部位的桥连接较弱。显微CT重建图像进一步说明,模型组缝隙相对较宽,愈伤组织较小。模型组较假手术组骨体积/组织体积(BV/TV)、愈伤组织面积、BALP、BGP含量、CD31阳性表达率、VEGF、MMP9、Notch1、HES1、HEY1蛋白水平均显著下降,CTX-Ⅰ含量显著升高,差异有统计学意义(P<0.05); 山奈酚组较模型组骨折部位的桥连接改善,缝隙相对变窄,BV/TV、愈伤组织面积、BALP、BGP、CD31阳性表达率、VEGF、MMP9、Notch1、HES1、HEY1蛋白水平显著升高,CTX-Ⅰ含量显著下降,差异有统计学意义(P<0.05),而抑制剂组与山奈酚组以上指标结果相反; DAPT恢复了山奈酚对骨折大鼠血管生成和骨折愈合的影响。结论:山奈酚可促进骨折大鼠血管生成和骨折愈合,其机制与Notch信号通路的激活相关。
Abstract:
Objective:To explore the effects of kaempferol on fracture healing and angiogenesis in rats by regulating Notch signal pathway.Methods:Eighteen rats were randomly selected and recorded as sham operation group,and the rest rats were used to construct fracture rat model.The fracture rats that were successfully modeled were randomly divided into model group,kaempferol group(intraperitoneal injection of 100 mg/(kg?d)kaempferol),inhibitor group(intraperitoneal injection of 5 mg/(kg?d)Notch signal pathway inhibitor DAPT),and kaempferol+inhibitor group(intraperitoneal injection of 100 mg/(kg?d)kaempferol and 5 mg/(kg?d)DAPT)for 8 consecutive weeks,18 rats in each group.The fracture healing was analyzed by computerized tomography; bone metabolism was detected by ELISA; the expression of CD31 was detected by immunofluorescence staining; and Western Blot was applied to detect the expression of bone formation markers(BMP2,SOX9),angiogenesis markers(VEGF and MMP9)and Notch signal pathway proteins.Results:X-ray images showed that the bridge connection of fracture site in model group was weak.The micro CT reconstruction images further showed that the gap in model group was relatively wide and the callus was smaller.Compared with Sham operation group,the bone volume/tissue volume(BV/TV),callus area,BALP,BGP contents,CD31 positive expression rate,VEGF,MMP9,Notch1,HES1,and HEY1 protein levels in model group decreased obviously,the CTX-Ⅰ content increased obviously(P<0.05); compared with model group,the bridge connection of fracture site in kaempferol group was improved,and the gap was relatively narrow,the BV/TV,callus area,BALP,BGP,CD31 positive expression rate,VEGF,MMP9,Notch1,HES1,HEY1 protein levels increased obviously,the CTX-Ⅰ content decreased obviously(P<0.05),the results of the above indexes in DAPT group and kaempferol group were opposite; DAPT restored the effects of kaempferol on angiogenesis and fracture healing in fracture rats.Conclusion:kaempferol can promote angiogenesis and fracture healing and angiogenesis in fracture rats,and its mechanism is related to the activation of Notch signal pathway.

参考文献/References:

[1] ZHANG L,JIAO G,REN S,et al.Exosomes from bonemarrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion[J].Stem Cell Res Ther,2020,11(1):38-64.
[2] HO-SHUI-LING A,BOLANDER J,RUSTOM L E,et al.Bone regeneration strategies:engineered scaffolds,bioactive molecules and stem cells current stage and future perspectives[J].Biomaterials,2018,180:143-162.
[3] DING L,GU S,ZHOU B,et al.Ginsenoside compound K enhances fracture healing via promoting osteogenesis and angiogenesis[J].Front Pharmacol,2022,13:855393.
[4] WONG S K,CHIN K Y,IMA-NIRWANA S.The osteoprotective effects of kaempferol:the evidence from in vivo and in vitro studies[J].Drug Des Devel Ther,2019,13:3497-3514.
[5] ADHIKARY S,CHOUDHARY D,AHMAD N,et al.Dietary flavonoid kaempferol inhibits glucocorticoid-induced bone loss by promoting osteoblast survival[J].Nutrition,2018,53:64-76.
[6] KAN T,HE Z,DU J,et al.Irisin promotes fracture healing by improving osteogenesis and angiogenesis[J].J Orthop Translat,2022,37:37-45.
[7] YANG Z,FENG L,WANG M,et al.Sesamin promotes osteoporotic fracture healing by activating chondrogenesis and angiogenesis pathways[J].Nutrients,2022,14(10):2106-2112.
[8] LI L,TANG P,ZHOU Z,et al.GIT1 regulates angiogenic factor secretion in bone marrow mesenchymal stem cells via NF-κB/Notch signalling to promote angiogenesis[J].Cell Prolif,2019,52(6):e12689-e126105.
[9] 唐晓旭,张志乾,李福琴,等.ADAM10在骨髓间充质干细胞成骨分化及胫骨骨折愈合中的作用及可能机制[J].中国比较医学杂志,2023,33(10):23-31.
[10] HUANG J,QI Z.MiR-21 mediates the protection of kaempferol against hypoxia/reoxygenation-induced cardiomyocyte injury via promoting Notch1/PTEN/AKT signaling pathway[J].PLoS One,2020,15(11):e0241007.
[11] ZHOU G,LI C,ZHANG R,et al.Kaempferol inhibits hepatic stellate cell activation by regulating miR-26b-5p/Jag1 axis and Notch pathway[J].Front Pharmacol,2022,13:881855.
[12] 李汪洋,熊辉.桃红四物汤早期干预对大鼠骨折愈合中间充质干细胞归巢的影响[J].中国骨伤,2022,35(4):367-374.
[13] ZHAO J,WU J,XU B,et al.Kaempferol promotes bone formation in part via the mTOR signaling pathway[J].Mol Med Rep,2019,20(6):5197-5207.
[14] 李静,尉娜,刘亚美,等.γ-分泌酶抑制剂DAPT阻断Notch通路并纠正脑卒中后抑郁大鼠Th17/Treg失衡[J].中国病理生理杂志,2021,37(3):393-399.
[15] FENG L,ZHANG J F,SHI L,et al.MicroRNA-378 suppressed osteogenesis of MSCs and impaired bone formation via inactivating Wnt/β-catenin signaling[J].Mol Ther Nucleic Acids,2020,21:1017-1028.
[16] KAMENAGA T,KURODA Y,NAGAI K,et al.Cryopreserved human adipose-derived stromal vascular fraction maintains fracture healing potential via angiogenesis and osteogenesis in an immunodeficient rat model[J].Stem Cell Res Ther,2021,12(1):110-123.
[17] MARTINIAKOVA M,BABIKOVA M,MONDOCKOVA V,et al.The role of macronutrients,micronutrients and flavonoid polyphenols in the prevention and treatment of osteoporosis[J].Nutrients,2022,14(3):523-552.
[18] SANTINONI C S,NEVES APC,ALMEIDA B F M,et al.Bone marrow coagulated and low-level laser therapy accelerate bone healing by enhancing angiogenesis,cell proliferation,osteoblast differentiation,and mineralization[J].J Biomed Mater Res A,2021,109(6):849-858.
[19] YANG L,YANG J,PAN T,et al.Liraglutide increases bone formation and inhibits bone resorption in rats with glucocorticoid-induced osteoporosis[J].J Endocrinol Invest,2019,42(9):1125-1131.
[20] COMPSTON J.Glucocorticoid-induced osteoporosis:an update[J].Endocrine,2018,61(1):7-16.
[21] MA L,ZHAO X,LIU Y,et al.Dihydroartemisinin attenuates osteoarthritis by inhibiting abnormal bone remodeling and angiogenesis in subchondral bone[J].Int J Mol Med,2021,47(3):04855.
[22] DING Z,YU F,SUN Y,et al.ORMDL3 promotes angiogenesis in chronic asthma through the ERK1/2/VEGF/MMP9 pathway[J].Front Pediatr,2022,9:708555.
[23] CHEN P,ZHANG G,JIANG S,et al.Mechanosensitive Piezo1 in endothelial cells promotes angiogenesis to support bone fracture repair[J].Cell Calcium,2021,97:102431.
[24] PENG Y,WU S,LI Y,et al.Type H blood vessels in bone modeling and remodeling[J].Theranostics,2020,10(1):426-436.

备注/Memo

备注/Memo:
基金项目:河北省科学技术成果(20200628)
更新日期/Last Update: 2025-03-10