Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China.
Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Front Immunol. 2022 May 2;13:870981. doi: 10.3389/fimmu.2022.870981. eCollection 2022.
The iliac vein can be severely stenosed and occluded due to thrombosis, tumor compression, or an anatomical abnormality. Such occlusion could result in limb swelling, venous claudication, and persistent leg ulcers. Its devastating sequelae heavily impact patients lifestyles and the social economy. Due to a lack of a stable and easy-to-operate iliac vein occlusion (IVO) model, its underlying molecular mechanism and pathophysiological process has not been completely understood. Melatonin (MLT) plays a critical role in anti-inflammation, but the potential protective effect of melatonin on venous dysfunction induced by IVO has not been revealed. In this study, a mouse model of IVO was established to study the effects of MLT on injured veins. The results of laser speckle images and Evans blue showed that MLT inhibited venous permeability in an IVO mouse model. Furthermore, MLT suppressed inflammation of surrounding tissues close to the affected vein by inhibiting the mRNA levels of TNF-α, IL-1α, and MCP-1. In addition, endothelial injury was inhibited by MLT using zonula occludens protein-1 (ZO-1) staining. Taken together, we elucidated the therapeutic effect of MLT on vascular dysfunction induced by IVO, mainly by inhibiting the TNF-α, IL-1α, and MCP-1 mRNA levels, improving endothelial function, and inhibiting vascular leakage.
髂静脉可因血栓形成、肿瘤压迫或解剖异常而严重狭窄和闭塞。这种闭塞可导致肢体肿胀、静脉跛行和持续性腿部溃疡。其破坏性的后果严重影响了患者的生活方式和社会经济。由于缺乏稳定且易于操作的髂静脉闭塞（IVO）模型，其潜在的分子机制和病理生理过程尚未完全了解。褪黑素（MLT）在抗炎中起着关键作用，但褪黑素对 IVO 引起的静脉功能障碍的潜在保护作用尚未被揭示。在这项研究中，建立了一个 IVO 小鼠模型来研究 MLT 对受损静脉的影响。激光散斑图像和 Evans 蓝的结果表明，MLT 抑制了 IVO 小鼠模型中的静脉通透性。此外，MLT 通过抑制 TNF-α、IL-1α 和 MCP-1 的 mRNA 水平抑制了受影响静脉附近周围组织的炎症。此外，通过封闭蛋白-1（ZO-1）染色，MLT 抑制了内皮损伤。总之，我们阐明了 MLT 对 IVO 引起的血管功能障碍的治疗作用，主要通过抑制 TNF-α、IL-1α 和 MCP-1 的 mRNA 水平、改善内皮功能和抑制血管渗漏。
