时珍国医国药2025，Vol.36Issue(10)：1807-1815,9.DOI:10.70976/j.1008-0805.SZGYGY-2025-1002
桃红四物汤对骨折愈合中HIF-1α通路与H型血管-MSCs耦联的影响
Investigating the early intervention effect of Taohong Siwu Decoction(桃红四物汤)on rats' H-Type Vessel-MSC coupling in fracture healing via the HIF-1α/VEGF/FAK pathway
摘要
Abstract
Objective To investigate the mechanism by which Taohong Siwu Decoction(桃红四物汤,TSD)promotes fracture healin-gof H-type vessel-mesenchymal stem cell(MSC)coupling via the HIF-1α/VEGF/FAK signaling pathway at the early stage.Methods Forty-eight mice were randomly divided into four groups:the model group,2-methoxyestradiol(2-ME2)group,TSD group,and TSD+2-ME2 group,with 12 mice in each group.Then a left femoral shaft fracture model was established.The TSD and TSD+2-ME2 groups received intragastric administration of TSD solution(0.58 g/ml),while the 2-ME2 and TSD+2-ME2 groups were given intraperitoneal injections of 2-ME2(4.2 mg/ml)on days 1,3 and 5 after surgery.The other groups received saline injec-tions.Safranin O-Fast Green staining was used to observe cartilage,immunofluorescence staining to assess H-type vessel formation,and qPCR and Western blot(WB)to detect the gene and protein expressions of HIF-1α,VEGF,and FAK.An H-ECs-MSCs co-culture system was established with four groups:Control group,TSD serum group,TSD+2-ME2 serum group,and 2-ME2 group.Cell viability and angiogenesis were assessed using CCK-8,Transwell migration,and tube formation assays.Results Compared with the model group,the 2-ME2 group showed reduced cartilage area,lower fluorescence intensity of H-type vessels,and decreased expres-sion of HIF-1α,VEGF,and FAK(P＜0.05).The TSD and TSD+2-ME2 groups demonstrated increased cartilage area,a higher proportion of H-type vessels,and elevated HIF-1α,VEGF,and FAK levels(P＜0.01),with the TSD group outperforming the TSD+2-ME2 group.HIF-1α and VEGF peaked at day 14 and then slightly decreased,while FAK continued to rise(P＜0.01).Cell via-bility,MSC migration,and angiogenesis were elevated in the TSD serum group(P＜0.05).Conclusion TSD promotes fracture healing at early stage by activating the HIF-1α/VEGF/FAK signaling pathway,facilitating the H-type vessel formation and MSC migration coupling,thereby shortening fracture healing time.关键词
骨折愈合/桃红四物汤/H型血管/间充质干细胞/缺氧诱导因子-1α/血管内皮生长因子/粘附斑激酶Key words
Fracture healing/Taohong Siwu Decoction(桃红四物汤)/H-type vessel/Mesenchymal stem cells/HIF-1α/VEGF/FAK分类
医药卫生引用本文复制引用
马泽冰,刘怡兵,卢承印,罗志强,熊辉,李汪洋,曹向阳..桃红四物汤对骨折愈合中HIF-1α通路与H型血管-MSCs耦联的影响[J].时珍国医国药,2025,36(10):1807-1815,9.基金项目
湖南省自然科学基金(2024JJ6349) （2024JJ6349）
湖南省中医药管理局项目(B2023036) （B2023036）
湖南省教育厅项目(22B0369) （22B0369）
湖南省荷尖人才项目(2023RC3167) （2023RC3167）
国家自然科学基金预研项目(Z2023YYJJ10) （Z2023YYJJ10）
河南省中医药学科领军人才项目(2021) （2021）
