The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Zhongshan Road 321, Nanjing 210008, Jiangsu, PR China.
Thromb Res. 2013 Jan;131(1):e31-8. doi: 10.1016/j.thromres.2012.11.002. Epub 2012 Nov 28.
The experiment was designed to analyze whether and how nitric oxide (NO) microbubbles facilitates deep vein thrombosis (DVT) resolution in a rat model.
DVT was induced by ligation of the inferior vena cava (IVC) and left common iliac vein (LCIV) in a rat model. The rats were sacrificed at day 2 and day 8 after ligation. NO was wrapped in lipidic microbubbles which were injected (1.6ml/kg) via tail vein twice a day. Thrombi isolated from IVC were measured by weight (g) and weight length ratio (g/cm).The histological analysis of LCIV indicated that platelets and inflammatory cells aggregation were reduced. The expression of vascular cell adhesion molecule-1 (VCAM-1) was quantified by immunohistochemical (IHC) staining and western blot. The coagulation functions including prothrombin time (PT), thrombin time (TT),activated partial thromboplastin time (APTT) and fibrinogen (FIB) were tested as well.Vein walls from IVC were processed by real-time polymerase chain reaction (RT-PCR) for several endothelial genes including matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), thrombomodulin (TM), and endothelial nitric oxide synthase (eNOS). The thrombus weight and the expression of VCAM-1 significantly decreased after NO microbubbles treatment. The expression of these endothelial genes were significantly up-regulated by NO micribubbles. There was no statistical difference among the groups in terms of PT, APTT, and TT.
NO microbubbles significantly facilitate DVT resolution in a rat model. The antithrombotic properties of NO microbubbles may be associated with reduced platelets and inflammatory cells aggregation, enhanced collagen turnover and stimulus to an anticoagulant condition of endothelium.
本实验旨在分析一氧化氮（NO）微泡是否以及如何促进大鼠深静脉血栓（DVT）的溶解。
采用结扎大鼠下腔静脉（IVC）和左髂总静脉（LCIV）的方法诱导 DVT。结扎后第 2 天和第 8 天处死大鼠。NO 包裹在脂质微泡中，通过尾静脉每天注射两次（1.6ml/kg）。通过重量（g）和重量长度比（g/cm）测量从 IVC 分离的血栓。LCIV 的组织学分析表明血小板和炎症细胞聚集减少。通过免疫组织化学（IHC）染色和 Western blot 定量测定血管细胞黏附分子-1（VCAM-1）的表达。还测试了凝血功能，包括凝血酶原时间（PT）、凝血酶时间（TT）、活化部分凝血活酶时间（APTT）和纤维蛋白原（FIB）。通过实时聚合酶链反应（RT-PCR）对包括基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、血栓调节蛋白（TM）和内皮型一氧化氮合酶（eNOS）在内的几种内皮基因对 IVC 血管壁进行处理。NO 微泡处理后血栓重量和 VCAM-1 的表达显著降低。NO 微泡显著上调这些内皮基因的表达。在 PT、APTT 和 TT 方面，各组之间无统计学差异。
NO 微泡显著促进大鼠 DVT 的溶解。NO 微泡的抗血栓特性可能与血小板和炎症细胞聚集减少、胶原周转增强以及刺激内皮抗凝状态有关。
