目的 研究注射用丹参多酚酸(SAFI)与阿司匹林联合应用抑制血小板聚集作用和对凝血功能的影响,为临床中西药合理联合用药提供实验依据。方法 利用断尾法评价联合用药对小鼠尾部出血时间的影响;采用酶标仪法测定药物对二磷酸腺苷(ADP)、花生四烯酸(AA)、胶原(collagen)、凝血酶(thrombin)4种诱导剂作用下正常大鼠的血小板最大聚集率;测定凝血4项来评价联合用药对小鼠体内凝血功能的影响。结果 出血时间:联合用药后SAFI对阿司匹林作用的断尾小鼠出血时间无明显影响。抗血小板聚集:与对照组相比,SAFI、阿司匹林均可显著抑制ADP、胶原、AA和凝血酶诱导的血小板聚集(P<0.01);联合用药后SAFI可进一步增强阿司匹林抗ADP、胶原、AA和凝血酶诱导血小板聚集的效果(P<0.01,P<0.05)。凝血功能:联合用药后SAFI降低阿司匹林作用的凝血酶时间。结论 SAFI与阿司匹林联合应用可增强抗凝效果,并且不增加阿司匹林的出血风险。
Abstract
OBJECTIVE To explore the curative effect of combination therapy with salvianolate injection (SAFI) and aspirin on anti-platelet aggregation and blood coagulation function, provide the experimental evidence for clinical consequence use of combination therapy with traditional Chinese medicine and western medicine. METHODS The bleeding time was measured by cutting tail evaluating of combination of drugs; platelet maximum aggregation rate induced by ADP, AA, collagen and thrombin in rats was determined by absorbance method using a microplate reader; blood coagulation of the four indicators were measured by the semiautomatic blood agglutination instrument. RESULTS SAFI had nearly no effects on aspirin group′s bleeding time. The effect on blood platelets aggregation compared with control group, SAFI group and aspirin group could significantly reduce platelet aggregation induced by ADP, AA, collagen and thrombin in normal rats(P<0.01). Combinative group could significantly increase aspirin group′s anti-platelet aggregation induced by ADP, AA, collagen and thrombin in normal rats(P<0.01,P<0.05). Coagulation function SAFI can reduced aspirin group′s TT after the combination therapy. CONCLUSION SAFI can increase anticoagulation effect of aspirin, and have no effect on aspirin′s bleeding risk.
关键词
注射用丹参多酚酸 /
阿司匹林 /
联合用药 /
出血风险
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Key words
salvianolate injection (SAFI) /
aspirin /
combination therapy /
bleeding risk
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中图分类号:
R969.4
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参考文献
[1] OHIRA T, ISO H. Cardiovascular disease epidemiology in Asia[J]. Circulation J,2013, 77(7): 1646-1652.
[2] LU Z Y, ZHONG N S. Internal Medicine(内科学)[M]. Vol 7. Beijing: People′s Medical Publishing House,2008:779.
[3] HUANG Y,YAN D. Research progress of aspirin resistance[J]. J Southeast Univ(东南大学学报:医学版),2015, 34(3):459-462.
[4] GAO X M. Chinese Pharmacy(中药学) [M]. Beijing: People′s Medical Publishing House,2000:1087-1089.
[5] MIAO Y, GAO Z H, XU F, et al. Clinical observation on salvianolate for the treatment of angina pectoris in coronary heart disease with heart-blood stagnation syndrome[J]. Tradit Chin Drug Res Pharmacol (中国新药与临床药理),2006, 16(2):140-144.
[6] CHEN X L, GU R Y, ZHANG Y H, et al. Effects of salvianolic acid B on inflammatory cytokines in atherosclerosis rats [J]. Acta Univ Tradit Med Sin Pharmacol Shanghai(上海中药药大学学报), 2011, 25(1):63-67.
[7] LIU L, LI J, ZHANG Y, et al. Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor: evidence from clinic to laboratory[J]. Thromb Res, 2014, 134(4): 866-876.
[8] PATRONO C. Aspirin as an antiplatelet drug [J]. N Engl J Med,1994,330 (18): 1287-1294.
[9] WAN Y J, ZHUANG P W, ZHANG Y J. Antithrombotic activity of formononetin sodium and its mechanism[J]. Chin J New Drugs(中国新药杂志),2016,25(12): 1355-1358.
[10] KURZ K D,MAIN B W,SANDUSKY G E. Rat model of arterialthrombosis induced by ferric chloride [J]. Thromb Res, 1990, 60(4): 269-280.
[11] RODVIEN R, MIELKE C. Role of platelets in hemostasis and thrombosis [J]. West J Med,1976, 125: 181-186.
[12] COUGHLIN S R. How the protease thrombin talks to cells [J]. Proc Natl Acad Sci USA,1999, 96(20): 11023-11027.
[13] KAHN M L, ZHENG Y W, HUANG W, et al. A dual thrombin receptor system for platelet activation [J]. Nature,1998, 394(6694): 690-694.
[14] BERGMEIER W, STEFANINI L. Novel molecules in calcium signaling in platelets [J]. J Thromb Haemost, 2009, 7(1):187-190.
[15] PATRONO C. Aspirin as an antiplatelet drug [J]. N Engl J Med,1994,330 (18):1287-1294.
[16] CHEN Y H, DU G H, ZHANG J T. Salvianolic acid B protects brain against injuries caused by ischemia-reperfusion in rats [J]. Acta Pharmacol Sin(中国药理学报), 2000, 21(5): 463-466.
[17] LUAN H, KAN Z, XU Y. Rosmarinic acid protects against experimental diabetes with cerebral ischemia: relation to inflammation response [J]. J Neuroinflamm,2013, 10(28): 1742-1752.
[18] WANG M X,LIU Y Y,HU B H,et al. Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory disturbance in rat mesentery [J]. World J Gastroen,2010, 16(42): 5306-5316.
[19] WU H L,LI Y H,LIN Y H,et al. Salvianolic acid B protects human an endothelial cells from oxidative stress damage a possible protective role of glucose-regulated protein 78 induction [J]. Cardiovascular Res, 2009,81(1): 148-158.
[20] ZHU H B,ZOU L B,TIAN J W,et al. SMND-309,a novelderivative of salvianolic acid B,protects rat brains ischemia and reperfusion injury by targeting the JAK2/STAT3 pathway [J]. Eur J Pharmacol, 2013, 714(1): 23-31.
[21] ZHANG N,KANG T,XIA Y,et al. Effects of salvianolic acid B on survival,self-renewal and neuronal differentiation of bone marrow derived neural stem cells [J]. Eur J Pharm, 2012, 697(1): 32-39.
[22] DI PAOLO G, DE CAMOLLI P. Phosphoinositides in cell regulation and membrane dynamices[J]. Nature, 2006, 443(7112): 651-657.
[23] HECK J N, MELLMAN D L, LING K, et al. A conspicuous connection: structure defines function for the phosphatidylinositol-phosphate kinase family[J]. Crit Rev Biochem Mol Biol, 2007, 42(1):1539.
[24] HU J R,JIANG H,LIU X Q. Research progress of treatment of clopidogrel combined with aspirin [J]. J China Pharm(中国药房), 2013, 24(8): 750-753.
[25] YANG H Y, WANG X L. Research progress of antiplatelet drugs[J]. Chin Pharm J(中国药学杂志), 2012, 47(4):250-254.
[26] WANG Z Y, LI J Z, RUAN C G, et al.Thrombosis & Hemostasis Basic Principles & Clinical Practice(血栓与止血基础理论与临床)[M]. Shanghai:Shanghai Scientific & Technical Publishers,2004:103-107.
[27] SU M, LIANG H C, MENG J, et al. Investigation of Zingiber officinale carbo on coagulation function and TXB2,6-keto-PGFla in asthenia cold and blood deficiency syndrome rats [J]. Chin J Exp Tradit Med Form(中国药理与临床),2013, 19(9):190.
[28] ZHONG L Y, ZHENG H, GONG Q F,et al. Initial study on pharmacodynamic substance with haemostasis in charred japanese thistle herb [J]. Chin J Tradit Chin Med Pharm(中华中医药杂志),2011, 26(1): 147-149.
[29] XING J J, CAO T T, YANG F,et al. The research progress of Tannin compounds [J]. Heilongjiang Med J(黑龙江医药),2011, 5(24): 776-780.
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脚注
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基金
国家科技重大专项资助项目(2012zx09101202)
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