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在大鼠深静脉血栓形成模型中,黄芩苷通过SIRT1/NF-κB信号通路促进内皮祖细胞的迁移和血管生成,但阻碍血栓形成。

Baicalin promotes migration and angiogenesis of endothelial progenitor cells but impedes thrombus formation via SIRT1/NF-κB signaling in a rat model of deep vein thrombosis.

作者信息

Xie Jinfeng, Liao Yonggui, Wang Dile

机构信息

Department of Vascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Histol Histopathol. 2025 Apr;40(4):547-554. doi: 10.14670/HH-18-799. Epub 2024 Jul 26.

DOI:10.14670/HH-18-799
PMID:39290181
Abstract

BACKGROUND

Deep vein thrombosis (DVT) is the third most prevalent vascular disease worldwide, seriously threatening human health. Baicalin, a flavonoid isolated from the roots of , has been identified to play a crucial role in various vascular diseases. The study aimed to explore the efficacy and underlying mechanisms of baicalin in DVT.

METHODS

Endothelial progenitor cells (EPCs) were differentiated from peripheral blood mononuclear cells isolated from rat bone marrow. Dil-ac-LDL/FITC-UEA-1 double staining and flow cytometry analysis were conducted for the identification of EPCs. The angiogenesis and migration of EPCs were tested by a tube formation assay and Transwell assay, respectively. DVT rat models were established by stenosis of the inferior vena cava (IVC). After the euthanasia of rats, thrombi in the IVC were collected and weighed, and histological alterations in IVC tissue were measured by H&E staining. The protein levels of SIRT1, p-P65, and p65 in rat IVC tissues were quantified via western blotting.

RESULTS

EPCs used in this study displayed a spindle-like shape and were positive for endothelial cell-specific markers, suggesting the phenotypic characteristics of EPCs. Baicalin enhanced the migratory and angiogenetic abilities of EPCs . For experiments, baicalin reduced thrombus weight and mitigated DVT formation in model rats. Moreover, baicalin activated SIRT but repressed NF-κB signaling in IVC tissues of DVT rats.

CONCLUSION

Baicalin facilitates migration and angiogenesis of EPCs but impedes thrombus formation via regulation of SIRT1/NF-κB signaling in DVT model rats.

摘要

背景

深静脉血栓形成(DVT)是全球第三大常见血管疾病,严重威胁人类健康。黄芩苷是从黄芩根中分离出的一种黄酮类化合物,已被证实在多种血管疾病中发挥关键作用。本研究旨在探讨黄芩苷在DVT中的疗效及潜在机制。

方法

从大鼠骨髓分离的外周血单核细胞中分化出内皮祖细胞(EPCs)。采用Dil-ac-LDL/FITC-UEA-1双重染色和流式细胞术分析鉴定EPCs。分别通过管腔形成试验和Transwell试验检测EPCs的血管生成和迁移能力。通过下腔静脉(IVC)狭窄建立DVT大鼠模型。大鼠安乐死后,收集IVC中的血栓并称重,通过苏木精-伊红(H&E)染色测量IVC组织的组织学改变。通过蛋白质印迹法定量大鼠IVC组织中SIRT1、p-P65和p65的蛋白水平。

结果

本研究中使用的EPCs呈纺锤形,内皮细胞特异性标志物呈阳性,表明具有EPCs的表型特征。黄芩苷增强了EPCs的迁移和血管生成能力。在实验中,黄芩苷降低了模型大鼠的血栓重量并减轻了DVT的形成。此外,黄芩苷激活了DVT大鼠IVC组织中的SIRT,但抑制了NF-κB信号通路。

结论

在DVT模型大鼠中,黄芩苷通过调节SIRT1/NF-κB信号通路促进EPCs的迁移和血管生成,但阻碍血栓形成。

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本文引用的文献

1
Astragaloside IV induces endothelial progenitor cell angiogenesis in deep venous thrombosis through inactivation of PI3K/AKT signaling.黄芪甲苷通过抑制 PI3K/AKT 信号通路诱导深静脉血栓形成中的血管生成。
Histol Histopathol. 2024 Sep;39(9):1149-1157. doi: 10.14670/HH-18-704. Epub 2024 Jan 5.
2
Protective Role of Endothelial SIRT1 in Deep Vein Thrombosis and Hypoxia-induced Endothelial Dysfunction Mediated by NF-κB Deacetylation.内皮 SIRT1 通过 NF-κB 去乙酰化在深静脉血栓形成和缺氧诱导的内皮功能障碍中的保护作用。
Inflammation. 2023 Oct;46(5):1887-1900. doi: 10.1007/s10753-023-01848-9. Epub 2023 Jun 24.
3
Baicalin Reduces Renal Inflammation in Mesangial Proliferative Glomerulonephritis through Activation of Nrf2/ARE and PI3K/AKT Pathways.
黄芩苷通过激活 Nrf2/ARE 和 PI3K/AKT 通路减轻系膜增生性肾小球肾炎的肾脏炎症。
Discov Med. 2023 Jun;35(176):372-382. doi: 10.24976/Discov.Med.202335176.38.
4
Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis.口服直接凝血酶抑制剂或口服因子 Xa 抑制剂与传统抗凝剂治疗深静脉血栓形成的比较。
Cochrane Database Syst Rev. 2023 Apr 14;4(4):CD010956. doi: 10.1002/14651858.CD010956.pub3.
5
Baicalin Relieves LPS-Induced Lung Inflammation via the NF-κB and MAPK Pathways.黄芩素通过 NF-κB 和 MAPK 通路缓解 LPS 诱导的肺炎症。
Molecules. 2023 Feb 16;28(4):1873. doi: 10.3390/molecules28041873.
6
Downregulation of miR-125a-5p Promotes Endothelial Progenitor Cell Migration and Angiogenesis and Alleviates Deep Vein Thrombosis in Mice Via Upregulation of MCL-1.miR-125a-5p 的下调通过上调 MCL-1 促进内皮祖细胞迁移和血管生成,并减轻小鼠深静脉血栓形成。
Mol Biotechnol. 2023 Oct;65(10):1664-1678. doi: 10.1007/s12033-023-00676-4. Epub 2023 Feb 4.
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Baicalin Alleviates Thrombin-Induced Inflammation in Vascular Smooth Muscle Cells.黄芩苷减轻凝血酶诱导的血管平滑肌细胞炎症。
Biomed Res Int. 2022 Jan 21;2022:5799308. doi: 10.1155/2022/5799308. eCollection 2022.
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Baicalin ameliorates cigarette smoke-induced airway inflammation in rats by modulating HDAC2/NF-κB/PAI-1 signalling.黄芩苷通过调节组蛋白去乙酰化酶 2/核因子-κB/纤溶酶原激活物抑制剂-1 信号通路改善香烟烟雾诱导的大鼠气道炎症。
Pulm Pharmacol Ther. 2021 Oct;70:102061. doi: 10.1016/j.pupt.2021.102061. Epub 2021 Jul 24.
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Antithrombotic effects of Huanglian Jiedu decoction in a rat model of ischaemia-reperfusion-induced cerebral stroke.黄连解毒汤对缺血再灌注诱导脑卒中风大鼠的抗血栓作用。
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