异甜菊醇对大鼠心肌缺血再灌注损伤的心电图影响

1、异甜菊醇对大鼠心肌缺血再灌注损伤的心电图影响         【摘要】【关键词】  异甜菊醇 心肌缺血再灌注损伤 线粒体ATP敏感性钾通道   Abstract  Objective  To observe the  effect of isostevioside on the electrocardiogram induced by ischemia and reperfusion in rat, and to explore the relations

2、hip between the cardioprotective effect of isostevioside and mitochondrial ATP- sensitive channels(mitoKATP ). Methods The myocardial injury was induced by ligation of the left coronary lasting for 30 min followed by relief for 90 min. Isosteviol (0.5, 1.0 and 2.0 mg/kg, iv) and 5-Hydroxydecanoate (

3、10mg/kg, iv) were administrated 1015 min prior to ischemia-reperfusion. The changes of ST segment and the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) were monitored during experiment. ResultsThe changes of ST segment and the incidence of VT and VF in rats pretreated w

4、ith isosteviol were significantly less than ischemia-reperfusion group. In 5-HD+ST-1 group, the changes of ST segment and the incidence of VT and VF were less than those in isosteviol pretreated group. Conclusion Isosteviol has protective effect on myocardial injury and arrhythmia induced by ischemi

5、a-reperfusion in rats; it may be mediated by mitoKATP   Key words  Isosteviol  Myocardial ischemia-reperfusion injury   Mitochondrial ATP-sensitive potassium channel   心肌缺血再灌注损伤是一个复杂的病理生理变化过程，可引起心功能衰竭、心律失常和心肌细胞死亡。目前许多的研究已证实ATP敏感性钾通道（mitochondrial ATP-sensitive

6、 potassium channel，mitoKATP）开放能有效抑制心肌缺血复灌损伤的作用。mitoKATP通道的活性受多种因素调节, 其中细胞内三磷酸腺苷（ATP）浓度是主要因素之一。在生理情况下mitoKATP通道保持关闭状态。当细胞内ATP水平下降时KATP通道趋向于开放。异甜菊醇（isosteviol, ent-16-ketobeyeran-19-oic acid）是甜菊苷的酸水解产物，研究表明：它能抑制大鼠肝细胞线粒体氧化磷酸化有关酶的活性，减少ATP的合成，有利于开放mitoKATP。且有研究发现异甜菊醇有松弛大鼠血管平滑肌作用,该作用可能也与钾通道开放有关1。通过在体大鼠研究，

7、从功能、形态和酶学等方面已证实异甜菊醇具有保护心肌缺血再灌注损伤的作用2。本试验旨在观察异甜菊醇对心肌缺血再灌注损伤大鼠的心电图影响，并探讨它的作用与mitoKATP之间的关系。   1  材料与方法   1.1  材料   健康成年SD大鼠 ，体重250350 g，雌雄兼用，购自南京医科大学医学实验动物中心。   异甜菊醇按Mosetting等3报道的方法制备，纯度为99.5%。 使用前用NaOH溶液溶解后，用HCL将溶液pH值调整到7.37.5，再用生理盐水稀释到所需浓度。5羟基癸酸（5-H

8、ydroxydecanoate，5-HD ）购于Sigma公司，为白色粉末。   1.2  实验方法   根据大鼠体重、性别随机分为模型对照组(IR)、异甜菊醇0.5 mg/kg组（ST1）、1.0 mg/kg组（ST2）、2.0 mg/kg组（ST3）、5羟基癸酸 10 mg/kg组（5-HD）和5羟基癸酸 10 mg/kg +异甜菊醇1.0 mg/kg组（5-HD+ST2）,每组1012只。将各组大鼠心脏冠状动脉结扎30 min后,再灌注90 min。IR 、ST1、ST2和ST3组大鼠在结扎前10 min经颈静脉依次给予生理盐水1ml/k

9、g、异甜菊醇0.5 mg/kg、1 mg/kg、和2.0 mg/kg；5-HD组在结扎前15 min经颈静脉给予5羟基癸酸（10 mg/kg）； 5-HD+ST2组在结扎前15 min经颈静脉给予5-HD （10 mg/kg）, 5 min后给予异甜菊醇（1.0 mg/kg）。给药体积均为1.0 ml/kg。            按照文献 Wong KL, Chan P, Yang HY, et al. Isosteviol acts on potassium channels to rela

10、x isolated aortic strips of Wistar ratJ.Life Sci, 2004,74(19):2379-23872 李永芳,许德义.异甜菊醇对大鼠在体心肌缺血再灌注损伤的保护作用J.中国药理学与毒理学杂志，2005，19(5):343-3463Mosettig E, Nes WR. Stevioside-the structure of the aguconJ.J Org Chem, 1955,20:884-8994Ockaili RA, Bhargava P, Kukreja KC. Chemical preconditioning with 3-nitropr

11、opionic acid in hearts role of mitochondrial K(ATP) channelJ.Am J Physiol heart Circ Physiol, 2001,280(5): 4065 Cryer HG. Therapeutic approaches for clinical ischemia and reperfusion injuryJ. Shock, 1997, 8:26-32 6 Miyata H, Lakatta EG, Stern MD, et al. Relation of mitochondrial and cytosolic free calcium to cardiac myocyte recovery after exposure to anxiaJ. Circ Res, 1992,71:605-6137 Holmuhamedov EL，Jovanovic S, Dzeja PP, et al. Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial functionJ. Am J Physiol, 1998,2