Zhang Yuanyuan, Li Long, Zhao Yazheng, Han Han, Hu Yang, Liang Di, Yu Boyang, Kou Junping
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China.
Int J Biol Sci. 2017 May 15;13(5):630-639. doi: 10.7150/ijbs.18485. eCollection 2017.
Arterial thrombosis and its related diseases are major healthcare problems worldwide. Blebbistatin is an inhibitor of myosin II, which plays an important role in thrombosis. The aim of our study is to explore the effect and potential mechanism of blebbistatin on arterial thrombosis. A ferric chloride (FeCl) solution at a concentration of 5% was used to induce carotid artery thrombosis in mice. Immunohistochemistry and immunofluorescence staining were used to detect the expression or activation of non-muscle myosin heavy chain IIA (NMMHC IIA), tissue factor (TF), GSK3β and NF-κB. Blebbistatin (1 mg/kg, i.p.) significantly reduced carotid artery thrombosis induced by FeCl solution in mice, inhibited NMMHC IIA expression and impeded TF expression via the GSK3β-NF-κB signalling pathway in mouse arterial vascular tissues. The present study demonstrates that blebbistatin may impede TF expression partly via the Akt/GSK3β-NF-κB signalling pathways in the endothelium in a FeCl model, shedding new insights into the pathogenesis of arterial thrombosis and providing new clues for the development of antithrombotic drugs.
动脉血栓形成及其相关疾病是全球主要的医疗保健问题。肌球蛋白抑制剂blebbistatin对血栓形成具有重要作用。本研究旨在探讨blebbistatin对动脉血栓形成的影响及其潜在机制。采用5%的三氯化铁（FeCl）溶液诱导小鼠颈动脉血栓形成。通过免疫组织化学和免疫荧光染色检测非肌肉肌球蛋白重链IIA（NMMHC IIA）、组织因子（TF）、糖原合成酶激酶3β（GSK3β）和核因子κB（NF-κB）的表达或激活情况。Blebbistatin（1 mg/kg，腹腔注射）可显著减轻FeCl溶液诱导的小鼠颈动脉血栓形成，抑制小鼠动脉血管组织中NMMHC IIA的表达，并通过GSK3β-NF-κB信号通路阻碍TF的表达。本研究表明，在FeCl模型中，blebbistatin可能部分通过内皮细胞中的Akt/GSK3β-NF-κB信号通路阻碍TF的表达，为动脉血栓形成的发病机制提供了新的见解，并为抗血栓药物的开发提供了新的线索。
