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利伐沙班和低分子量肝素抗血管生成行为的研究。

Investigation of the antiangiogenic behaviors of rivaroxaban and low molecular weight heparins.

作者信息

Yavuz Celal, Caliskan Ahmet, Karahan Oguz, Yazici Suleyman, Guclu Orkut, Demirtas Sinan, Mavitas Binali

机构信息

Department of Cardiovascular Surgery, Medical School of Dicle University, Diyarbakir, Merkez, Turkey.

出版信息

Blood Coagul Fibrinolysis. 2014 Jun;25(4):303-8. doi: 10.1097/MBC.0000000000000019.

Abstract

Antithrombotic agents play important roles in the prophylactic and therapeutic management of many cardiovascular disorders. Therefore, many researchers have focused on developing new strategies for anticoagulation. New oral anticoagulants and factor Xa inhibitors are products of such research. Although they are identified as advantageous, there are limited data available about their multisystemic interactions. Thus, the antiangiogenic behaviors of oral factor Xa inhibitors and low molecular weight heparins (LMWHs) were investigated in this study. The chick chorioallantoic membrane (CAM) model was designed to investigate the antiangiogenic potential of new oral factor Xa inhibitors (rivaroxaban) and LMWHs (enoxaparin sodium and tinzaparin sodium). Four different molar concentrations (10, 10, 10, and 10 μmol/l) were studied for each drug. Each concentration was studied on 20 fertilized eggs. Vessel structures were evaluated under a stereoscopic microscope, and vessel formation was scaled according to previous literature. Both enoxaparin and tinzaparin sodium have increased antiangiogenic efficacy on CAM in a dose-dependent manner. However, this increased efficacy did not reach significant levels (average score < 0.5). On the contrary, while rivaroxaban showed dose-dependent antiangiogenic properties similar to enoxaparin and tinzaparin, a significant average antiangiogenic score (0.7) was detected at 10 μmol/l concentrations. New oral anticoagulants seem to be more favorable. However, their safety for the cardiovascular system needs to be clarified through microsystem studies on, for example, angiogenesis.

摘要

抗血栓药物在许多心血管疾病的预防和治疗管理中发挥着重要作用。因此,许多研究人员专注于开发新的抗凝策略。新型口服抗凝药和Xa因子抑制剂就是这类研究的成果。尽管它们被认为具有优势,但关于其多系统相互作用的数据有限。因此,本研究调查了口服Xa因子抑制剂和低分子量肝素(LMWHs)的抗血管生成行为。鸡胚绒毛尿囊膜(CAM)模型旨在研究新型口服Xa因子抑制剂(利伐沙班)和LMWHs(依诺肝素钠和替扎肝素钠)的抗血管生成潜力。每种药物研究了四种不同的摩尔浓度(10、10、10和10 μmol/l)。每种浓度在20枚受精卵上进行研究。在立体显微镜下评估血管结构,并根据先前文献对血管形成进行评分。依诺肝素和替扎肝素钠对CAM的抗血管生成功效均呈剂量依赖性增加。然而,这种增加的功效未达到显著水平(平均评分<0.5)。相反,虽然利伐沙班显示出与依诺肝素和替扎肝素相似的剂量依赖性抗血管生成特性,但在10 μmol/l浓度下检测到显著的平均抗血管生成评分(0.7)。新型口服抗凝药似乎更具优势。然而,它们对心血管系统的安全性需要通过例如血管生成的微系统研究来阐明。

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