深静脉血栓形成IκK/IκB/NF-κB信号传导通路及中医药干预机制的研究
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摘要
目的：从核转录因子1κB、抑制因子κκB及其激酶(IκK/IκB/NF-κB)信号传导通路的角度,深入探讨深静脉血栓形成(DVT)的病理本质,并探讨中药干预DVT的作用靶点及干预环节,为DVT的防治提供新的思路。
方法：通过实验研究,以下腔静脉结扎法建立DVT大鼠模型,采用中药抵当汤为治疗组,穿王消炎片、复方丹参片和血栓模型组为对照组,并设假手术组。免疫组化及荧光定量PCR法观察大鼠血管内皮细胞及静脉壁中NF-κBP65、NF-KBP50、IκBa及其激酶IκKα(I kappa B kinase a)和IκKβ(I kappa B kinaseβ)的表达水平,探讨其变化规律,HE染色光镜观察下腔静脉病理形态学改变,扫描电镜及投射电镜观察静脉血管内皮细胞损伤程度。
结果：实验研究显示血栓模型组大鼠血管内皮细胞及静脉壁中NF-KBP65、NF-κBP50、IκKα、IκKβ的表达较假手术组明显增强,IκBa的表达较假手术组减弱,工腔静脉病理形态学改变较假手术组严重。抵当汤能通过阻断IκKα、IκKβ的活化,抑制IκBa磷酸化及降解,从而降低NF-KBP65、NF-KBP50在血管内皮细胞中及血管壁中的表达水平,改善大鼠下腔静脉的病理改变程度。
结论：IκK/IκB/NF-κB信号传导通路在DVT的发生、发展过程中起重要作用,介导或直接参与血管内皮细胞的相互作用以及血管壁的损伤,中药可以通过干预IκK/IκB/NF-κB信号传导系统来抑制炎症反应及血栓形成,达到防治DVT的目的。
Objective:To investigate the pathogenesis of deep venous thrombosis(DVT) from the Signal transduction of Nuclear factor kappaB/Inhibitory kappaB/Inhibitory kappaB kinases (IκK/IκB/NF-κB), and interventional mechanism of Chinese Herbs on DVT, in order to provide new idea for prevention and cure of DVT.
Methods:In the experiment, uses the vena cava inferior ligation law to establish the deep phlebothrombosis big mouse model.Wistar rats were divided into five groups which included Di Dang Tang group, Chuan Wang Xiao Yan tablets group, Fu Fang Dan Shen tablets group, model group, sham group. Then to observe the level of NF-KBP65、NF-κBP50、IκKα、IκBαkinases IκKα(I kappa B kinase a) and IκKβ(I kappa B kinaseβ) in vascular endothelial cell(VEC) and Vessel wall, through through immunohistochemical method and Quantitative PCR method, discussing their Variation,observe the pathological character under the light microscope, the electron microscope and transmission electron microscope.
Results:Experiment shows that higher level of NF-κBP65、NF-κBP50、IκKα、IκKβin vascular endothelial cell(VEC) and Vessel wall of model group,lower level of IκBa in VEC and Vessel wall of model group, and more severe pathological changes in model group.Di Dang Tang can effectively reduce the expressions of NF-κBP65、NF-κBP50、IκKαand IκKβ, improve the expressions of IκBa and the pathological changes.
Conclutions:The Signal transduction of IκK/IκB/NF-κB may participate in genesis and development of DVT, introduce the reciprocity of VECs and injury of vein. The Chinese herbs can intervene the Signal transduction of IκK/IκB/NF-κB to suppress inflammatory reaction and thrombosis.
方法：通过实验研究,以下腔静脉结扎法建立DVT大鼠模型,采用中药抵当汤为治疗组,穿王消炎片、复方丹参片和血栓模型组为对照组,并设假手术组。免疫组化及荧光定量PCR法观察大鼠血管内皮细胞及静脉壁中NF-κBP65、NF-KBP50、IκBa及其激酶IκKα(I kappa B kinase a)和IκKβ(I kappa B kinaseβ)的表达水平,探讨其变化规律,HE染色光镜观察下腔静脉病理形态学改变,扫描电镜及投射电镜观察静脉血管内皮细胞损伤程度。
结果：实验研究显示血栓模型组大鼠血管内皮细胞及静脉壁中NF-KBP65、NF-κBP50、IκKα、IκKβ的表达较假手术组明显增强,IκBa的表达较假手术组减弱,工腔静脉病理形态学改变较假手术组严重。抵当汤能通过阻断IκKα、IκKβ的活化,抑制IκBa磷酸化及降解,从而降低NF-KBP65、NF-KBP50在血管内皮细胞中及血管壁中的表达水平,改善大鼠下腔静脉的病理改变程度。
结论：IκK/IκB/NF-κB信号传导通路在DVT的发生、发展过程中起重要作用,介导或直接参与血管内皮细胞的相互作用以及血管壁的损伤,中药可以通过干预IκK/IκB/NF-κB信号传导系统来抑制炎症反应及血栓形成,达到防治DVT的目的。
Objective:To investigate the pathogenesis of deep venous thrombosis(DVT) from the Signal transduction of Nuclear factor kappaB/Inhibitory kappaB/Inhibitory kappaB kinases (IκK/IκB/NF-κB), and interventional mechanism of Chinese Herbs on DVT, in order to provide new idea for prevention and cure of DVT.
Methods:In the experiment, uses the vena cava inferior ligation law to establish the deep phlebothrombosis big mouse model.Wistar rats were divided into five groups which included Di Dang Tang group, Chuan Wang Xiao Yan tablets group, Fu Fang Dan Shen tablets group, model group, sham group. Then to observe the level of NF-KBP65、NF-κBP50、IκKα、IκBαkinases IκKα(I kappa B kinase a) and IκKβ(I kappa B kinaseβ) in vascular endothelial cell(VEC) and Vessel wall, through through immunohistochemical method and Quantitative PCR method, discussing their Variation,observe the pathological character under the light microscope, the electron microscope and transmission electron microscope.
Results:Experiment shows that higher level of NF-κBP65、NF-κBP50、IκKα、IκKβin vascular endothelial cell(VEC) and Vessel wall of model group,lower level of IκBa in VEC and Vessel wall of model group, and more severe pathological changes in model group.Di Dang Tang can effectively reduce the expressions of NF-κBP65、NF-κBP50、IκKαand IκKβ, improve the expressions of IκBa and the pathological changes.
Conclutions:The Signal transduction of IκK/IκB/NF-κB may participate in genesis and development of DVT, introduce the reciprocity of VECs and injury of vein. The Chinese herbs can intervene the Signal transduction of IκK/IκB/NF-κB to suppress inflammatory reaction and thrombosis.
引文
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