Feng Yaping, Zhang Fuxian, Niu Luyuan, Zhang Mingyi
Department of Vascular Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, P.R. China.
Blood Coagul Fibrinolysis. 2016 Jul;27(5):531-41. doi: 10.1097/MBC.0000000000000567.
The study aimed to observe the therapeutic effect of simvastatin in a deep vein thrombosis (DVT) animal model and conduct a preliminary study into its mechanism. A total of 72 New Zealand white rabbits were randomly divided into control group (n = 18), low molecular weight heparin (LMWH) group (n = 18), simvastatin group (n = 18), and simvastatin + LMWH group (n = 18). A posterior vena cava thrombus model was established and interventions were administered according to the group procedures. Blood plasma was sampled before and 3, 7, and 14 days after the intervention when the vena cava (including thrombus) specimen was collected. Specimens were weighed, histopathologically examined, and monitored for changes in venous wall inflammation. Concentrations of P-selectin, plasminogen activator inhibitor (PAI-1), and the urokinase plasminogen activator (u-PA) activity were measured with enzyme-linked immunosorbent assay. P-selectin expression in the venous wall was measured with immunohistochemistry, and quantitative PCR detected the changes of local PAI-1/u-PA expression. Simvastatin and LMWH reduced the weight of the thrombus and promoted thrombus dissolution. Simvastatin significantly inhibited the systemic and local expression of P-selectin, whereas LMWH was inhibitory only at the late stage of the acute phase. Plasma active concentration and local gene expression of PAI-1 was inhibited by simvastatin, whereas for u-PA; it was promoted at the early stage of the acute phase, but inhibited in the late stage. Simvastatin inhibited the expression of inflammatory mediators, reduced the DVT inflammatory response, alleviated inflammatory injury and reduced thrombus formation. Simvastatin may provide a beneficial adjuvant therapy for DVT.
该研究旨在观察辛伐他汀在深静脉血栓形成（DVT）动物模型中的治疗效果，并对其作用机制进行初步研究。将72只新西兰白兔随机分为对照组（n = 18）、低分子肝素（LMWH）组（n = 18）、辛伐他汀组（n = 18）和辛伐他汀+LMWH组（n = 18）。建立后腔静脉血栓模型，并根据分组程序进行干预。在干预前以及干预后3、7和14天采集血浆，同时收集腔静脉（包括血栓）标本。对标本进行称重、组织病理学检查，并监测静脉壁炎症的变化。采用酶联免疫吸附测定法测量P-选择素、纤溶酶原激活物抑制剂（PAI-1）的浓度以及尿激酶纤溶酶原激活物（u-PA）的活性。采用免疫组织化学法测量静脉壁中P-选择素的表达，定量PCR检测局部PAI-1/u-PA表达的变化。辛伐他汀和LMWH均减轻了血栓重量并促进了血栓溶解。辛伐他汀显著抑制P-选择素的全身和局部表达，而LMWH仅在急性期后期具有抑制作用。辛伐他汀抑制PAI-1的血浆活性浓度和局部基因表达，而对于u-PA，在急性期早期促进其表达，但在后期抑制其表达。辛伐他汀抑制炎症介质的表达，减轻DVT炎症反应，减轻炎症损伤并减少血栓形成。辛伐他汀可能为DVT提供有益的辅助治疗。
