蛇毒血小板抑制因子对心肌缺血再灌注损伤大鼠血小板膜糖蛋白VI表达以及血液流变的影响及意义

doi:10.12092/j.issn.1009-2501.2020.01.007

中国临床药理学与治疗学 ›› 2020, Vol. 25 ›› Issue (1): 49-54.doi: 10.12092/j.issn.1009-2501.2020.01.007

蛇毒血小板抑制因子对心肌缺血再灌注损伤大鼠血小板膜糖蛋白VI表达以及血液流变的影响及意义

吴娟¹，张鹤²，冯桂林³

¹皖南医学院病理生理教研室，芜湖 241000，安徽； ²皖南医学院第一附属医院弋矶山医院呼吸内科，芜湖 241000，安徽； ³皖南医学院第一附属医院弋矶山医院血管外科，芜湖 241000，安徽

收稿日期:2019-09-27 修回日期:2019-12-22 出版日期:2020-01-26 发布日期:2020-02-11
通讯作者: 张鹤，男，主治医师，研究方向：肺癌。 E-mail：anzai1983@sina.com
作者简介:吴娟，女，硕士研究生，研究方向：蛇毒基础与应用，心血管病理生理学。 Tel：13605530252　 E-mail：wj198505@sina.cn
基金资助:
2018年安徽省高校自然科学研究项目（KJ2018A0269）

Agkistrodon halys venom platelet inhibitor inhibits GPVI expression and changes hemorheology in rats with acute myocardial ischemia reperfusion injury

WU Juan ¹, ZHANG He ², FENG Guilin ³

¹ Department of Pathophysiology, Wannan Medical College,Wuhu 241000, Anhui, China; ² Department of Respiratory Medcine, Yijishan Hospital of Wannan Medical College, Wuhu 241000, Anhui, China; ³Department of Vascular Surgery, Yijishan Hospital of Wannan Medical College, Wuhu 241000, Anhui, China

Received:2019-09-27 Revised:2019-12-22 Online:2020-01-26 Published:2020-02-11

摘要/Abstract

摘要： 目的:探讨皖南蝮蛇毒血小板抑制因子(agkistrodon halys venom platelet inhibitor，AHV-PI)对心肌缺血再灌注损伤(myocardial ischemia reperfusion injury，MIRI)、大鼠血小板膜糖蛋白VI（GPVI）表达以及血液流变的影响及意义。方法:SD雄性大鼠30只，随机分为假手术组（6只）、心肌缺血再灌注损伤模型组（6只）和AHV-PI实验组（18只），实验采用结扎大鼠左冠状动脉前降支方法制备大鼠MIRI模型。AHV-PI实验组根据大鼠舌下静脉注射AHV-PI的剂量（0.05，0.1，0.2 mg/kg）再依次分为低、中、高三组，每组6只，RM6240生物信号采集处理系统监测心电变化。蛋白质免疫印迹法（Western blot）监测AHV-PI干预下，大鼠GPVI的表达水平。血栓弹力仪（TEG5000）描记凝血时间（R）、血凝块形成时间（K）、Alpha角度（A）和凝血最大幅度（MA）。采用比浊法检测血小板聚集率。结果:与MIRI模型组相比，AHV-PI中剂量实验组和高剂量实验组GPVI表达水平明显降低（P＜0.05）；R值和K值明显延长，A值和MA值减小（P＜0.05）；血小板聚集时间、聚集幅度和聚集率均明显降低（P＜0.05）。结论:AHV-PI可显著抑制MIRI大鼠GPVI的表达并可改善大鼠心肌损伤相关的血液流变学特性，进而弱化其损伤过程。

关键词: 蝮蛇毒血小板抑制因子, 心肌缺血再灌注损伤, 血液流变, 血小板膜糖蛋白VI

Abstract: AIM:To explore effect and meaning of Agkistrodon halys venom platelet inhibitor on GPVI expression and hemorheology in rats with acute myocardial ischemia reperfusion injury. METHODS:Thirty matched SD male rats were randomly divided into sham operation group (6 rats), myocardial ischemia-reperfusion injury(MIRI) model group(6 rats) and agkistrodon halys venom platelet inhibitor (AHV-PI) group(18 rats). The AHV-PI experimental group was divided into low, middle and high dose groups according to the dose of AHV-PI injected into sublingual vein (0.05, 0.1, 0.2 mg/kg), with 6 rats in each group. Electrocardiogram(ECG) changes of rats were monitored by RM6240 biological signal collection and processing system. Western blot was used to monitor the expression of platelet membrane glycoprotein VI (GPVI) in rats under the intervention of AHV-PI. Blood coagulation time (R), blood clots forming time (K), Alpha Angle (A), and maximum amplitude of blood coagulation (MA) were assayed by Thrombelastography (TEG5000).Platelet aggregation rate was measured by turbidimetry. RESULTS:Compared with MIRI model group, the expression level of GPVI AHV-PI medium dose experimental group and high dose experimental group were significantly decreased (P＜0.05), and the R and K values were significantly prolonged, while the A value and MA values were significantly decreased (P＜0.05). Platelet aggregation time, aggregation amplitude and aggregation rate were significantly decreased (P＜0.05). CONCLUSION: AHV-PI can significantly inhibit the expression of GPVI in MIRI rats and improve the hemorheological properties related to myocardial injury in rats, thus weakening the injury process.

Key words: platelet inhibitor from Agkistrodon halys venom, myocardial ischemia reperfusion injury, hemorheology, glycoprotein VI

中图分类号:

R965.2

吴娟，张鹤，冯桂林. 蛇毒血小板抑制因子对心肌缺血再灌注损伤大鼠血小板膜糖蛋白VI表达以及血液流变的影响及意义[J]. 中国临床药理学与治疗学, 2020, 25(1): 49-54.

WU Juan, ZHANG He, FENG Guilin. Agkistrodon halys venom platelet inhibitor inhibits GPVI expression and changes hemorheology in rats with acute myocardial ischemia reperfusion injury[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(1): 49-54.

参考文献

［1］Morishima I, Sone T, Okumura K, et al. Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction［J］. J Am College Cardiol, 2000, 36(4):1202-1209.
［2］Kloner RA, Dai W, Hale SL.No-reflow phenomenon. A new target for therapy of acute myocardial infarction independent of myocardial infarct size［J］. J Cardiovasc Pharmacol Therapeu, 2018, 23(3):273-276.
［3］Setiadi BM, Hartono B, Prakoso AB, et al. Antiplatelet for coronary artery disease in specific condition "No Size Fits All"［J］.Curr Pharm Des,2018,24(4):478-495.
［4］Induruwa I, Moroi M, Bonna A. Platelet collagen receptor Glycoprotein VI-dimer recognizes fibrinogen and fibrin through their D-domains, contributing to platelet adhesion and activation during thrombus formation［J］.Thromb Hemost, 2018,16(2): 389-404.
［5］Huang L, Zhang GB, Min ZX, et al. Agkistrodon halys venom platelet inhibitor, s influence on the arterial thrombosis and mechanism research［J］. Chin Clin Pharmacol Therapeu,2012,17(12):1355-1360.
［6］Ji N, Zhang GB, Huang L, et al. Effects of platelet inhibitor from Agkistrodon halys venom on artery thrombosis in rabbit ［J］. Chin J Clinl Pharmacol Therapeu, 2014,19(9):987-990.
［7］Kou XH, Qian ZY. Myocardial ischemia-reperfusion injury in rats model of improvement and evaluation［J］. J Chin Exp Animals, 2018,26(3): 311-316.
［8］Clemetson JM, Polgar J,Magnenat E, et al.The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcaR and the natural killer receptors［J］. J Biol Chem, 1999,274:29019-29024.
［9］Jandrotperrus M, Busfield S, Lagrue AH, et al. Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily［J］. Blood, 2000, 96(5):1798-1807.
［10］Jung SM,Tsuji K,Moroi M.GlycoproteinVI dimer as a major collagen-binding site of native platelets: direct evidence obtained with dimeric GPVI-specific Fabs［J］. Thromb Haemost, 2009,7(8):1347-1355.
［11］Watson SP, Herbert JM, Pollitt AY.GPVI and CLEC-2 in hemostasis and vascular integrity［J］. J Thromb Haemost, 2010,8(7):1456-1467.
［12］Zahid M, Loyau S, Bouabdelli M, et al. Design and reshaping of an scFv directed against human platelet glycoprotein VI with diagnostic potential ［J］. Anal Biochem, 2011,417(2): 274-282.
［13］Lei X, Reheman A, Hou Y,et al. Anfibatide, a novel GPIb complex antagonist, inhibits platelet adhesion and thrombus formation in vitro and in vivo in murine models of thrombosis［J］. Thromb Haemost ,2014,111 (2): 279-289.
［14］Matsui T, Fujimura Y, Titani K. Snake venom proteases affecting hemostasis and thrombosis［J］. Biochim Biophys Acta, 2000,1477(1/2):146-156.
［15］Lee BK, Durairaj A, Mehra A, et al. Hemorheological abnormalities in stable angina and acute coronary syndromes［J］.Clin Hemorheol Microcirc,2008, 39(1-4):43-51.
［16］Fracassi F, Vetrugno V, Mandurino-Mirizzi,et al. Effect of hemorheological parameters on myocardial injury after primary or elective percutaneous coronary intervention［J］. Coron Artery Dis,2018,29(8):638-646.
［17］Stettler GR, Sumislawski JJ, Moore EE,et al.Citrated kaolin thresholds for goal-directed therapy in injured patients receiving massive transfusion［J］.Trauma Acute Care Surg, 2018,85(4):734-740.
［18］Yuan HX, Zhang RJ, Qi M, et al. Thrombus elastic graph in the application of the patients after liver transplantation［J］. J Clin Liver Dis,2015,31(2)：253-255.
［19］Kuzniatsova N，Shantsila E，Blann A,et al. A contemporary viewpoint on "aspirin resistance"［J］. Ann Med,2012,44(8):773-783.
［20］Haji Aghajani M, Kobarfard F, Shojaei SP, et al. The impact of clopidogrel resistance on clinical outcome of Iranian patients undergoing percutaneous coronary intervention［J］. Iran J Pharm Res, 2018 Summer, 17(3):1099-1104.
［21］Zahid M,Loyau S, Bouabdelli M, et al. Design and reshaping of an scFv directed against human platelet glycoprotein VI with diagnostic potential［J］.Anal Biochem, 2011,417(2):274-282.

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蛇毒血小板抑制因子对心肌缺血再灌注损伤大鼠血小板膜糖蛋白VI表达以及血液流变的影响及意义

Agkistrodon halys venom platelet inhibitor inhibits GPVI expression and changes hemorheology in rats with acute myocardial ischemia reperfusion injury

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