Deep venous thrombosis(DVT)poses a major challenge to public health worldwide.Endothelial cell injury evokes in-flammatory and oxidative responses that contribute to thrombus formation.Tea polyphenol(TP)in the form of epigallocatechin-3-gal-late(EGCG)has anti-inflammatory and oxidative effect that may ameliorate DVT.However,the precise mechanism remains incom-pletely understood.The current study was designed to investigate the anti-DVT mechanism of EGCG in combination with warfarin(an oral anticoagulant).Rabbits were randomly divided into five groups.A DVT model of rats was established through ligation of the in-ferior vena cava(IVC)and left common iliac vein,and the animals were orally administered with EGCG,warfarin,or vehicle for sev-en days.In vitro studies included pretreatment of human umbilical vein endothelial cells(HUVECs)with different concentrations of EGCG for 2 h before exposure to hydrogen peroxide.Thrombus weight and length were examined.Histopathological changes were observed by hematoxylin-eosin staining.Blood samples were collected for detecting coagulation function,including thrombin and pro-thrombin times,activated partial thromboplastin time,and fibrinogen levels.Protein expression in thrombosed IVCs and HUVECs was evaluated by Western blot,immunohistochemical analysis,and/or immunofluorescence staining.RT-qPCR was used to determine the levels of AGTR-1 and VEGF mRNA in IVCs and HUVECs.The viability of HUVECs was examined by CCK-8 assay.Flow cyto-metry was performed to detect cell apoptosis and ROS generation was assessed by 2',7'-dichlorofluorescein diacetate reagent.In vitro and in vivo studies showed that EGCG combined with warfarin significantly reduced thrombus weight and length,and apoptosis in HUVECs.Our findings indicated that the combination of EGCG and warfarin protects HUVECs from oxidative stress and prevents ap-optosis.However,HIF-1α silencing weakened these effects,which indicated that HIF-1α may participate in DVT.Furthermore,HIF-1α silencing significantly up-regulated cell apoptosis and ROS generation,and enhanced VEGF expression and the activation of the PI3K/AKT and ERK1/2 signaling pathways.In conclusion,our results indicate that EGCG combined with warfarin modifies HIF-1α and VEGF to prevent DVT in rabbits through anti-inflammation via the PI3K/AKT and ERK1/2 signaling pathways.

LI Yan;GE Jing-Ping;MA Ke;YIN Yuan-Yuan;HE Juan;GU Jian-Ping

Department of Vascular and Interventional Radiology,Nanjing First Hospital,Nanjing Medical University,Nanjing 210006,China;Department of Acupuncture,Qinhuai District Hospital of Traditional Chinese Medicine,Nanjing 210000,China

中国天然药物

[1]LI Yan;GE Jing-Ping;MA Ke;YIN Yuan-Yuan;HE Juan;GU Jian-Ping-.The combination of EGCG with warfarin reduces deep vein throm-bosis in rabbits through modulating HIF-1α and VEGF via the PI3K/AKT and ERK1/2 signaling pathways)[J].中国天然药物,2022(09):679-690

incom,ferior,Thrombus,thrombosed,IVCs,AGTR,optosis

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