Mechanism of the protective effects of the combined treatment with rhynchophylla total alkaloids and sinapine thiocyanate against a prothrombotic state caused by vascular endothelial cell inflammatory damage

钩藤总碱与芥子碱硫氰酸酯联合应用对血管内皮细胞炎性损伤致血栓前状态的保护作用机制

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作者:Yunlun Li, Xinya Zhang, Wenqing Yang, Chao Li, Yanjun Chu, Haiqiang Jiang, Zhenzhen Shen

Abstract

The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs. Combined treatment with RTA and sinapine thiocyanate was demonstrated to reduce, to a varying extent, the mRNA and protein expression of NF-κB, TGF-β1, TF, PAR-1, PKC-α and PAI-1. Furthermore, combined treatment with RTA and sinapine thiocyanate was able to downregulate the expression of coagulation-related factors in injured VECs, thereby inhibiting the PTS induced by vascular endothelial injury. The underlying mechanism is partially associated with the TF-mediated activation of the thrombin-receptor signaling pathway that suppresses coagulation during inflammation and balances fibrinolysis in order to inhibit fibrin generation and deposition.

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