Feng Yaping, Lei Bo, Zhang Fuxian, Niu Luyuan, Zhang Huan, Zhang Mingyi
Department of Vascular Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Anesthesia Department, Beijing Haidian Maternal & Child Health Hospital, Beijing, China.
J Investig Med. 2017 Aug;65(6):999-1007. doi: 10.1136/jim-2017-000442. Epub 2017 Apr 25.
Deep venous thrombosis (DVT) is a common vascular disease and is closely linked to inflammation. Over the past decade, the potential antithrombotic effect of statins has been elucidated by clinical studies, primarily through focusing on DVT prevention. The effects of statins on DVT resolution and its underlying mechanisms have been rarely addressed. We established a rabbit model of the (IVC) venous thrombosis. After 48 hours, the rabbits were treated with saline, heparin, simvastatin, or simvastatin combined with heparin, respectively, for 14 days. The migration of inflammatory cells (neutrophils, monocytes, lymphocytes) in the thrombi and injured venous wall, the plasma levels of interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and P-selectin, and local expression of MCP-1 and P-selectin in the venous wall were evaluated by histology, immunohistochemistry, and ELISA examinations. Our data showed that compared with saline and heparin controls, monotherapy of simvastatin and the adjunctive therapy with simvastatin and heparin significantly improved the thrombus resolution and reduced inflammatory cells migration into the venous wall, the release of the inflammatory cell adhesion molecule (P-selectin), inflammatory chemokine (MCP-1) and pleiotropic proinflammatory cytokines (IL-6) into the blood, and the local expression of P-selectin and MCP-1 in the venous wall. Simvastatin targets anti-inflammatory pathways during the resolution phase of a thrombus, providing a therapeutic potential in DVT resolution and post-thrombotic syndrome prevention.
深静脉血栓形成（DVT）是一种常见的血管疾病，与炎症密切相关。在过去十年中，他汀类药物的潜在抗血栓作用已通过临床研究得到阐明，主要集中在DVT预防方面。他汀类药物对DVT溶解及其潜在机制的影响很少被提及。我们建立了下腔静脉（IVC）静脉血栓形成的兔模型。48小时后，分别用生理盐水、肝素、辛伐他汀或辛伐他汀联合肝素对兔子进行治疗，持续14天。通过组织学、免疫组织化学和酶联免疫吸附测定（ELISA）检查评估血栓和受损静脉壁中炎症细胞（中性粒细胞、单核细胞、淋巴细胞）的迁移、白细胞介素（IL）-6、单核细胞趋化蛋白1（MCP-1）和P-选择素的血浆水平，以及静脉壁中MCP-1和P-选择素的局部表达。我们的数据表明，与生理盐水和肝素对照组相比，辛伐他汀单药治疗以及辛伐他汀与肝素联合治疗显著改善了血栓溶解，并减少了炎症细胞向静脉壁的迁移、炎症细胞黏附分子（P-选择素）、炎症趋化因子（MCP-1）和多效促炎细胞因子（IL-6）向血液中的释放，以及静脉壁中P-选择素和MCP-1的局部表达。辛伐他汀在血栓溶解阶段靶向抗炎途径，为DVT溶解和预防血栓后综合征提供了治疗潜力。
