顾明;吴兴文;李芳萍;黄诗颖;张捷;刘源杰;张雪梅;

• 1:复旦大学药学院药理学教研室
• 2:上海市闸北区中心医院药剂科

摘要(Abstract)：

目的研究丹参素对单个大鼠心室肌细胞动作电位、L-型钙电流和ATP敏感性钾电流(I_(KATP))的影响,探讨丹参素在离子通道水平的药理机制。方法胶原酶急性酶解法分离单个大鼠心室肌细胞,采用全细胞膜片钳的方法,记录丹参素对动作电位、L-型钙电流和I_(KATP)的影响。结果丹参素可影响心室肌细胞动作电位时程(APD),并能使APD 25、APD 50和APD 90显著缩短;丹参素能够抑制L-型钙电流;丹参素可使I_(KATP)外向电流增大,此效应呈浓度依赖性。结论丹参素的心肌保护作用机制与抑制L-型钙电流和部分激活I_(KATP)外向电流有关。

关键词(KeyWords)： 丹参素;全细胞膜片钳;心室肌细胞;动作电位;L-型钙通道;ATP敏感性钾离子通道

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(No.30600108);; 上海市浦江计划(No.06PJ14018)

作者(Authors): 顾明;吴兴文;李芳萍;黄诗颖;张捷;刘源杰;张雪梅;

DOI: 10.19577/j.cnki.issn10074406.2010.01.001

参考文献(References)：

• [1]Zhao GR,Xiang ZJ,Ye TX,et al.Antioxidant activities of Salvia miltiorrhiza and Panax notoginseng[J].Food Chem,2006,99(4):767.
• [2]袁恒杰.丹参素药理作用研究新进展[J].中国医院药学杂志, 2006,26(5):604.
• [3]Lam FF,Yeung JH,Chan KM,et al.Relaxant effects of danshen aqueous extract and its constituent danshensu on rat coronary artery are mediated by inhibition of calcium channels[J].Vascul Pharmacol,2007,46 (4):271.
• [4]刘婷,秦彩玲,张毅,等.复方丹参方对肾上腺素血瘀模型大鼠血小板黏聚性及TXB2、6-Keto-PGF1α的影响[J].中国实验方剂学杂志,2004,10(4):35.
• [5]陈丽娜,朱晓新.丹参改善血液流变性的实验研究进展[J].中国中药杂志,2005,30(8):630.
• [6]Cao CM,Xia Q,Zhang X,et al.Salvia miltiorrhiza attenuates the changes in contraction and intracellular calcium induced by anoxia and reoxygenation in rat cardiomyocytes[J].Life Sci,2003,72(22):2451.
• [7]Wang W,Hu GY,Wang YP.Selective modulation of L-type calcium current by magnesium lithospermate B in guinea-pig ventricular myocytes [J].Life Sci,2006,78(26):2989.
• [8]Lu T,Hoshi T,Weintraub NL,et al.Activation of ATP-sensitive K~+ channels by epoxyeicosatrienoic acids in rat cardliac ventricular myocytes [J].J Physiol,2001,537(3):811.
• [9]Miura T,Miki T.ATP-sensitive K~+ channel openers:old drugs with new clinical benefits for the heart[J].Curr Vasc Pharmacol,2003,1 (3):251.
• [10]Kocic I,Hirano Y,Hiraoka M.Hypotonic stress increases efficacy of rilmakalim,but not pinacidil,to activate ATP-sensitive K(~+) current in guinea pig ventricular myocytes[J].J Pharmacol Sci,2004,95(2): 189.
• [11]Moncada GA,Kishi Y,Numano F,et al.Effects of acidosis and NO on nicorandil-activated K(ATP) channels in guinea-pig ventricular myocytes [J].Br J Pharmacol,2000,131(6):1097.
• [12]钱卫民,邓春玉,薛玉梅,等.丹参素对豚鼠心室肌细胞L-型钙通道的影响[J].岭南心血管病杂志,2002,8(4):276.
• [13]Sabbatini M,Leonardi A,Testa R,et al.Effect of calcium antagonists on glomerular arterioles in spontaneously hypertensive rats[J].Hypertension, 2000,35(3):775.
• [14]Michailova A,Saucerman J,Belik ME,et al.Modeling regulation of cardiac K_(ATP) and L-type Ca~(2+) currents by ATP,ADP,and Mg~(2+) [J].Biophys J,2005,88(3):2234.
• [15]Pollesello P,Mebazaa A.ATP-dependent potassium channels as a key target for the treatment of myocardial and vascular dysfunction[J].Curr Opin Crit Care,2004,10(6):436.
• [16]Oketani N,Kakei M,Ichinari K,et al.Regulation of K(ATP) channels by P(2Y) purinoceptors coupled to PIP(2) metabolism in guinea pig ventricular cells[J].Am J Physiol Heart Circ Physiol,2002,282 (2):H757.
• [17]Ashcroft FM,Gribble FM.New windows on the mechanism of action of K(ATP) channel openers[J].Trends Pharmacol Sci,2000,21(11): 439.
• [18]Fujita A,Kurachi Y.Molecular aspects of ATP-sensitive K~+ channels in the cardiovascular system and K~+ channel openers[J].Pharmacol Ther,2000,85(1):39.
• [19]Wu L,Qian H,Li Y,et al.Protective roles of puerarin and Danshensu on acute ischemic myocardial injury in rats[J].Phytomedicine,2007, 14(10):652.