The effects of dioscin on myocardial contraction and sodium-cal-cium exchanger

doi:10.13459/j.cnki.cjap.2016.03.005

Abstract

Abstract: Objective:To investigate the inotropic effects of dioscin (Dio)in rat isolated-heart and intracellular free calcium concentration in isolated rat ventricular myocytes and to explore its mechanism preliminarily. Methods:Left ventricle contractile function was measured using the Langendorff non-recirculating mode of isolated rat heart perfusion. Effects of dioscin and dioscin+SEA0400, sodium-calcium exchanger (NCX) inhibitor, were investigated by measuring left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP). Also, heart rate (HR), peak rate of rise/fall of left ventricular pressure (±dp/dt_max) of isolated rat heart were calculated; Effects of dioscin and SEA0400 on intracellular free calcium concentration in rat H9c2 cells were measured by Fluo3-AM and then detected the fluorescence intensity with confocal microscopy. Results:With 1 μmol/L dioscin, LVSP was significantly increased by 19.7% (P<0.01) and dp/dt_max was increased by 9.6%; With 1 μmol/L dioscin, the relative fluorescence intensity of intracellular free calcium concentrations were strong significantly(P<0.01). While in presence of SEA0400, the relative fluorescence intensity was changed to 17.09±0.63 (P<0.01) by 1 μmol/L dioscin. With 1 μmol/L dioscin, the relative fluorescence intensity was weak(P<0.01) without calcium or sodium in the extracellular fluid. Conclusion:Dioscin shows positive inotropic effect on isolated rat heart, enhancing the LVSP and +dp/dt_max; Dioscin increases the intracellular concentration of Ca²⁺ in the cardiac myocytes by increasing Na⁺ influx and facilitating the reverse mode of the sodium-calcium exchanger.

Key words: dioscin, myocardium, rat, positive inotropic effect, sodium-calcium exchanger

YANG Fan, HAN Yu, CONG Tian-shen, KANG Yi, LI Yan, SUN Kai, YIN Yong-qiang, LOU Jian-shi. The effects of dioscin on myocardial contraction and sodium-cal-cium exchanger[J]. CJAP, 2016, 32(3): 209-213.

References

[1] 徐毅, 罗卓卡, 黄霏霏, 等. 正性肌力药物作用靶点的研究进展[J]. 中国新药杂志, 2012, 21(3):268-272.
[2] Pott C, Eckardt L, Goldhaber JI. Triple Threat:The Na⁺/Ca²⁺ Exchanger in the Pathophysiology of Cardiac Arrhythmia, Ischemia and Heart Failure[J]. Curr Drug Targets, 2011, 12(5):737-747.
[3] Passos AG, Gondim AN, Roman-Campos D, et al. The positive inotropic effect of the ethyl acetate fraction from Erythrinavelutina leaves on the mammalian myocardium:the role of adrenergic receptors[J]. J Pharm Pharmacol, 2013, 65(6):928-936.
[4] Xie Z, Xie J. The Na/K-ATPase-mediated signal transduction as a target for new drug development[J]. Front Biosci, 2005, 10:3100-3109.
[5] Chen L, Xu Y, Li W, et al. The novel compound liguzinediol exerts positive inotropic effects in isolated rat heart via sarcoplasmic reticulum Ca²⁺ ATPase-dependent mechanism[J]. Life Sci, 2012, 91(11):402-408.
[6] 张伟锋, 刘宝山. 薯蓣皂苷的药理作用研究进展[J]. 世界中西医结合杂志, 2010, 5(6):543-545.
[7] 侯娟, 何文辉, 王明霞, 等. 薯蓣皂苷的药理作用[J]. 河北医药, 2004, 26(1):71.
[8] 王晓鹏, 陆羡. 薯蓣皂苷生物活性研究新进展[J]. 国外医学:中医中药分册, 2004, 26(3):138-141.
[9] 宋宇, 梁长青, 何忠梅, 等. 薯蓣皂苷元体外抗肿瘤作用的研究[J]. 中国肿瘤, 2004, 13(10):651-653.
[10] Hobai IA, O'Rourke B. The potential of Na⁺/Ca²⁺ exchange blockers in the treatment of cardiac disease[J]. Expert Opin Inv Drugs, 2004, 13(6):653-664.
[11] Birinyi P, Acsai K, Bányász T, et al. Effects of SEA0400 and KB-R7943 on Na⁺/Ca²⁺ exchange current and L-type Ca²⁺ current in canine ventricular myocytes[J]. NaunynSchmiedebergs Arch Pharmacol, 2005, 372(1):63-70.
[12] Matsuda T, Arakawa N, Takuma K, et al. SEA0400, a novel and selective inhibitor of the Na⁺-Ca²⁺ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models[J]. J Pharmacol Exp Ther, 2001, 298(1):249-256.
[13] Iwamoto T, Kita S, Uehara A, et al. Molecular determinants of Na⁺/Ca²⁺ exchange (NCX1) inhibition by SEA0400[J]. J Bio Chem, 2004, 279(9):7544-7553.
[14] 汪玲芳, 赵云茜, 高卫真, 等. 薯蓣皂苷增强大鼠缺血再灌注损伤后心肌抗氧化能力[J]. 中药药理与临床, 2009, 25(5):44-46.
[15] 胡长鹰, 于文喜. 山药皂苷及其对离体心脏缺血再灌注损伤的保护作用[J]. 食品工业科技, 2011, (2):309-312.
[16] Kaneko Y, Nakajima T, Irie T, et al. Ventricular fibrillation following bidirectional tachycardia due to digitalis toxicity[J]. Intern Med, 2011, 50(19):2243-2243.
[17] 刘静, 吴红, 丛恬(马先), 等. 薯蓣皂苷含药血清对大鼠心室肌细胞钠离子通道的影响[J]. 中草药, 2014, 45(16):2370-2374.
[18] Farkas AS, Acsai K, Nagy N, et al. Na⁺/Ca²⁺ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart[J]. Br J Pharmacol, 2008, 154(1):93-104.