18β-Glycyrrhetinic Acid Improves Cardiac Diastolic Function by Attenuating Intracellular Calcium Overload
18β-Glycyrrhetinic Acid Improves Cardiac Diastolic Function by Attenuating Intracellular Calcium Overload
复制标题
18 β-甘草次酸通过减轻细胞内钙超载来改善心脏舒张功能
DOI：
10.1007/s11596-020-2232-y
复制
发表时间：
2020-08-01
影响因子：
2.4
通讯作者：
Shuai, Xin-xin
中科院分区：
文献类型：
--
作者：
Han, Jun;Su, Guan-hua;Shuai, Xin-xin
雷诺嗪是一种晚期钠电流抑制剂，已被证明对心力衰竭有效。18 β-甘草次酸（18 β-GA）对晚钠电流也有类似的抑制作用。然而，它对舒张功能的影响仍然是未知的。本研究的目的是确定18 β-GA是否可以改善舒张功能，并探讨其可能的机制。将80只雄性Sprague道利（SD）大鼠随机分为A组、B组、C组、D组和E组。A组为正常心脏灌注组，B组为缺血再灌注组，C组为ATX-Ⅱ缺血再灌注组，D组为雷诺嗪组，E组为18 β-GA组。此外，建立了经主动脉缩窄（TAC）所致压力超负荷大鼠模型。术后第14天应用超声心动图和血流动力学评价心脏舒张功能。激光扫描共聚焦显微镜间接检测细胞内游离钙离子浓度的变化，以证实晚期钠电流的抑制。ATX-II干预缺血再灌注损伤组，5 μ mol/L雷诺嗪和5、10、20、40 μ mol/L 18 β-GA均能改善ATX-II诱导的心脏舒张功能障碍。630 mg/kg的葛根素片可改善压力超负荷大鼠的心脏舒张功能。18 β-GA和雷诺嗪对降低心肌细胞游离钙的作用相似。本研究表明，18 β-GA和Escherin可以改善Langendorff灌注大鼠心脏和压力超负荷大鼠缺血再灌注损伤引起的舒张功能障碍。其机制可能与抑制增强的晚钠电流有关。
Ranolazine, a late sodium current inhibitor, has been demonstrated to be effective on heart failure. 18 beta-glycyrrhetinic acid (18 beta-GA) has the similar inhibitory effect on late sodium currents. However, its effect on diastolic function is still unknown. This study aimed to determine whether 18 beta-GA can improve the diastolic function and to explore the underlying mechanisms. Eighty male Sprague Dawley (SD) rats of Langendorff model were randomly divided into the following groups: group A, normal cardiac perfusion group; group B, ischemia-reperfusion group; group C, ischemia-reperfusion with anemoniasulcata toxin II (ATX-II); group D, ranolazine group; and group E, 18 beta-GA group with four different concentrations. Furthermore, a pressure-overloaded rat model induced by trans-aortic constriction (TAC) was established. Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC. Changes of free intracellular calcium (Ca2+) concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents. With the intervention of ATX-II on ischemia reperfusion injury group, 5 mu mol/L ranolazine, and 5, 10, 20, 40 mu mol/L 18 beta-GA could improve ATX-II-induced cardiac diastolic dysfunction. 630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats. 18 beta-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes. The study demonstrates that 18 beta-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats. The mechanism may be attributed to the inhibition of enhanced late sodium currents.