Department of Biochemistry and Molecular Biology, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China; Department of Pharmacological Sciences, Key Laboratory of Major Metabolic Diseases and Nutritional Regulation of Anhui Department of Education, Hefei University of Technology, Hefei, China.
Department of Biochemistry and Molecular Biology, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China.
Pharmacol Res. 2019 Jun;144:167-180. doi: 10.1016/j.phrs.2019.04.013. Epub 2019 Apr 12.
Formation of thrombosis is associated with activation of platelets and endothelial cells. The effect of LongShengZhi Capsule (LSZ), a traditional Chinese medicine used for treatment of vascular diseases, on thrombosis was investigated in this study. BALB/c mice were induced thrombosis by injection of carrageenan while receiving pre or simultaneous LSZ treatment. We also compared the therapeutic effects of LSZ and clopidogrel on formed thrombi. LSZ inhibited carrageenan-induced thrombi in mouse tissue vessels. In addition, LSZ but not clopidogrel reduced formed thrombi with a short time window. The reduction of thrombi by LSZ was associated with reduced serum P-selectin, reduced expression of TNF-α and P-selectin and activated matrix metalloproteinase 2 expression in tissues. In vitro, LSZ decreased thrombin-induced human platelet clot retraction which was associated with inactivation of AKT and ERK1/2. LSZ also reduced adhesion of platelets or THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein or lipopolysaccharide. The anti-adherent actions of LSZ was attributed to reduction of oxidative stress, expression of platelet receptors (P2Y, PAR4 and CD36) and AKT activity in platelets. LSZ also reduced adhesion molecules or tissue factor but activated tissue factor pathway inhibitor expression in HUVECs. Taken together, our study demonstrates the antithrombotic properties of LSZ by reducing activation of platelets and endothelial cells, and suggests its potential application in clinics.
血栓形成与血小板和内皮细胞的激活有关。本研究探讨了用于治疗血管疾病的中药龙生蛭胶囊(LSZ)对血栓形成的影响。通过注射角叉菜胶诱导 BALB/c 小鼠血栓形成,同时给予 LSZ 预处理或同时治疗。我们还比较了 LSZ 和氯吡格雷对形成的血栓的治疗效果。LSZ 抑制了小鼠组织血管中的角叉菜胶诱导的血栓形成。此外,LSZ 而不是氯吡格雷可在短时间窗口内减少形成的血栓。LSZ 减少血栓形成与血清 P-选择素减少、TNF-α 和 P-选择素表达减少以及组织中激活的基质金属蛋白酶 2 表达减少有关。在体外,LSZ 减少了凝血酶诱导的人血小板凝块回缩,这与 AKT 和 ERK1/2 的失活有关。LSZ 还减少了由氧化低密度脂蛋白或脂多糖诱导的血小板或 THP-1 单核细胞与人脐静脉内皮细胞(HUVECs)的粘附。LSZ 的抗粘附作用归因于血小板中氧化应激、血小板受体(P2Y、PAR4 和 CD36)表达和 AKT 活性的减少,以及 HUVECs 中粘附分子或组织因子的减少,但组织因子途径抑制剂的表达增加。总之,我们的研究表明 LSZ 通过减少血小板和内皮细胞的激活具有抗血栓形成特性,并表明其在临床上的潜在应用。