Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.
Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Int J Mol Med. 2018 Aug;42(2):883. doi: 10.3892/ijmm.2018.3682. Epub 2018 May 16.
The present study aimed to investigate the effect of the expression of interleukin (IL)‑18 and related markers on deep venous thrombosis (DVT) to examine their correlation. Sprague‑Dawley rats of different models were established and were randomly assigned into three groups. The expression of IL‑18, nuclear factor (NF)‑κB and von Willebrand factor (vWF) were detected in blood samples. The inferior vena cava (IVC) was ligated to establish the DVT model. Rat IL‑18 overexpression and inhibition vectors were constructed. The expression levels of IL‑18 and related markers in the venous wall were compared between the model group and the control group using reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Following the culture of human umbilical vein endothelial cells (HUVECs), IL‑18 was added to the cells, following which the growth of the HUVECs, and changes in vWF and other endothelial functional markers were analyzed. The IVC model demonstrated complete thrombosis at 8 h and stable thrombosis at 24 h. At 24 h following model establishment, the expression levels of IL‑18, NF‑κB and vWF were high in the blood samples with the occurrence and development of thrombosis (P<0.05). The weight, length and weight/length ratio of thrombi in each model group showed significant differences from those in the control group (P<0.05) with the overexpression of IL‑18, and the expression levels of NF‑κB and vWF in venous tissues were altered with abnormal expression levels of IL‑18. IL‑18 damaged HUVECs and significantly increased viability in early‑stage apoptosis, promoted the upregulation of vWF and P‑selectin, and reduced tissue plasminogen activator. IL‑18 and the related markers were closely associated with the occurrence and development of DVT.
本研究旨在探讨白细胞介素(IL)-18 及其相关标志物的表达对深静脉血栓形成(DVT)的影响,以研究它们之间的相关性。建立了不同模型的斯普拉格-道利大鼠,并将其随机分为三组。检测血液样本中 IL-18、核因子(NF)-κB 和血管性血友病因子(vWF)的表达。结扎下腔静脉(IVC)建立 DVT 模型。构建大鼠 IL-18 过表达和抑制载体。采用逆转录-定量聚合酶链反应和 Western blot 分析比较模型组和对照组静脉壁中 IL-18 及相关标志物的表达水平。在培养人脐静脉内皮细胞(HUVECs)后,向细胞中添加 IL-18,分析 HUVECs 的生长以及 vWF 和其他内皮功能标志物的变化。IVC 模型在 8 小时时完全血栓形成,在 24 小时时稳定血栓形成。在模型建立后 24 小时,随着血栓形成的发生和发展,血液样本中 IL-18、NF-κB 和 vWF 的表达水平升高(P<0.05)。每个模型组的血栓重量、长度和重量/长度比与对照组相比均有显著差异(P<0.05),IL-18 过表达时,静脉组织中 NF-κB 和 vWF 的表达水平发生改变,IL-18 表达异常。IL-18 损伤 HUVECs,明显增加早期凋亡的细胞活力,促进 vWF 和 P-选择素的上调,并降低组织型纤溶酶原激活物。IL-18 及其相关标志物与 DVT 的发生和发展密切相关。