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

doi:10.12092/j.issn.1009-2501.2020.01.007

Abstract

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

CLC Number:

R965.2

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.

References

［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.

[1]	HUA Haiyan, YAN Jie, QIN Yufen. Experimental study of schisandrin B attenuates acute myocardial ischemia injury in rats by inhibiting cardiomyocyte apoptosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(8): 848-856.
[2]	CHEN Miao, ZHANG Xinjin, MENG Hongli, YANG Bei, SONG Lijuan, ZOU Chuannan, GUAN Yingxia. Therapeutic effect of bisoprolol combined with salvianolate on patients with coronary heart disease after PCI [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(4): 451-457.
[3]	DONG Wen-bin, YE Xiao-di, CHENG Min, WANG Jun-qing, ZHENG Gao-li. Protective effect of hydroxy safflower yellow A on myocardial ischemia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(9): 1001-1005.
[4]	FEI Xian-ming, CHEN Yan, WU Wan-fei, JIANG Lei, QIU Lian-nv, ZHOU Yong-lie. Effects of Agrimoni Pilosa aqueous extract on platelet aggregation, coagulation function and hemorheology [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(1): 10-16.
[5]	XU Tun-hai, WEN Ping, LIU Bin, ZHANG Xiao-yong, JIA Su-rong, TAO Xiao-hua. Effects of PIANTONG capsule fluid extract on hemorheology, thrombus formation in vitro and electroencephalogram of pain-stimulated animals [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(6): 601-608.
[6]	REN Chuan-yong, XU Liang. Observation for effect of alprostadil on uric albumin excretion of the patients with diabetic nephropathy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(7): 812-814.
[7]	ZHAO Qing-chao, HU Jiu-lue. Effect of Huoxuetongqiao patch in transdermal delivery on hemorheology indics and SOD and LPO in experimental cerebral hemorrhage rabbits [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(7): 772-775.
[8]	XU Peng-fu, KAN Hong-wei, HUANG Shi-fu, YANG Shi-you, CHEN Han. Research of anti-artery thrombosis mechanism of action and the effect of Xinshi injection on hemorheology in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(12): 1392-1395.
[9]	MIN Qing, BAI Yu-ting, ZHANG Zhi, SHI Lu-yi. Influence of hawthorn leaves flavonoids on electrocardiogram, nitrogen monoxidum and malondia1dehyde of myocardial ischemia reperfusion injury in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(7): 800-803.
[10]	LU Hua, LUAN Jia-jie, SONG Jian-guo. Influence of Yinxingdamo injection and Shuxuening injection on hemorhe-ology and plasma levels of superoxide dismutase, malondialdehyde and ni-trogen monoxidum in aged rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(5): 582-585.
[11]	ZHANG Le-Zhi, MEN De-Sheng, WEN Bao-Shu, LU Jin-Sheng, WEI Bin. Study on the mechanisms of Quyuningtong paster in treating acute soft tissue injury in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(9): 1026-1029.
[12]	XIA Chao-Hong, YANG Yu-Wen, WANG Xing, CHEN Yue-Yun. Clinical evaluation ofProstaglandin E1liposome in treatment ofPatients with unstable anginaPectoris [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2003, 8(4): 459-461.
[13]	WANG Chang-Sheng, YANG Jie-Ren, GUI Chang-Qing, DING Bai-Ping, SONG Jian-Guo. Effects of salvia miltiorrhiza injection on acute myocardial ischemia and hemorheology models of rat [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2002, 7(1): 30-32.