Decichine enhances hemostasis of activated platelets via AMPA receptors

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• 作者：Ling-Fang Huang^a ; ^b ; ¹ ; Hai-Lian Shi^a ; ¹ ; Bo Gao^a ; ^b ; Hui Wu^a ; Li Yang^a ; Xiao-Jun Wu^a ; ^{xiaojunwu320@126.com" class="auth_mail} ; Zheng-Tao Wang^a ; ^b ; ^c ; ^{wangzht@hotmail.com" class="auth_mail}
• 关键词：TA ; Tranexamic acid ; CMC ; Carboxymethylcellulose ; ADP ; adenosine diphosphate ; PT ; prothrombin time ; APTT ; activated partial thromboplastin time ; FIB ; fibrinogen concentration ; TT ; thrombin time ; PBS ; phosphate buffer saline ; TXB2 ; thromboxane B2 ; 6-keto-PGF1伪 ; 6-keto-prostaglandin F1伪 ; cAMP ; cyclic adenosine monophosphate ; PRP ; platelet-rich plasma ; PPP ; platelet-poor plasma ; EDTA ; Ethylenediaminetetraacetic acid ; CNQX ; 6-cyano-7-nitro-quinoxaline-2 ; 3-dione ; NBQX ; 2 ; 3-dihydroxy-6-nitro-7-sulfa
• 刊名：Thrombosis Research
• 出版年：May, 2014
• 年：2014
• 卷：133
• 期：5
• 页码：848-854
• 全文大小：1019 K

文摘

Introduction

Dencichine, one of the non-protein amino acids present in the roots of Panax notoginseng, has been found to shorten bleeding time of mice and increase the number of platelets. However, the exact underlying mechanisms have not been elucidated yet. This study was aimed to identify the hemostatic effect of dencichine and uncover its mechanisms.

Materials and methods

Hemostatic effect was assessed by measuring tail bleeding time and coagulation indices of rats. PT, APTT, TT and FIB concentration were measured using a Sysmex CA-1500 plasma coagulation analyzer. Platelet aggregation rate was determined by using a platelet aggregometer. Concentration of cyotosolic calcium was evaluated by Fluo-3 and levels of cyclic adenosine monophosphate (cAMP) and thromboxane A₂ (TXA₂) were measured by ELISA method.

Results and conclusion

Dencichine administered orally shortened tail bleeding time, reduced APTT and TT but increased the concentration of FIB in plasma in a dose-dependent manner. When induced with trap, dencichine could elevate the cytoplasmic concentration of calcium, and secretion of TXA₂ as well as the ratio of TXA₂ to PGI₂ from platelets. Meanwhile, it decreased the level of intracellular cAMP. However, CNQX could block the enhanced hemostatic effect of dencichine. These results suggested that dencichine exerted hemostatic function via AMPA receptors on platelets, therefore, facilitated coagulation cascade in a paracrine fashion by control of platelet cytosolic calcium influx, cAMP production and TXA₂ release. Current study may contribute to its clinical use in therapy of hemorrhage.