Department of Cardiology, Wuhan Fourth Hospital Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Curr Med Sci. 2020 Aug;40(4):654-661. doi: 10.1007/s11596-020-2232-y. Epub 2020 Aug 29.
Ranolazine, a late sodium current inhibitor, has been demonstrated to be effective on heart failure. 18β-glycyrrhetinic acid (18β-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 18β-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, 18β-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 (Ca) 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 µmol/L ranolazine, and 5, 10, 20, 40 µmol/L 18β-GA could improve ATX-II-induced cardiac diastolic dysfunction. 630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats. 18β-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes. The study demonstrates that 18β-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.
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。18β-甘草次酸（18β-GA）对晚期钠电流具有相似的抑制作用。然而，其对舒张功能的影响尚不清楚。本研究旨在确定 18β-GA 是否可以改善舒张功能，并探讨其潜在机制。80 只雄性 SD 大鼠随机分为以下 5 组：A 组，正常心脏灌注组；B 组，缺血再灌注组；C 组，缺血再灌注+海葵毒素 II（ATX-II）组；D 组，雷诺嗪组；E 组，用 4 个不同浓度的 18β-GA 预处理组。此外，建立了由主动脉缩窄（TAC）诱导的压力超负荷大鼠模型。TAC 术后 14 天，通过超声心动图和血流动力学评估舒张功能。通过激光共聚焦显微镜间接检测细胞内游离钙（Ca）浓度的变化，以确认晚期钠电流的抑制作用。在 ATX-II 干预缺血再灌注损伤组、5 μmol/L 雷诺嗪和 5、10、20、40 μmol/L 18β-GA 后，均可改善 ATX-II 诱导的心脏舒张功能障碍。630 mg/kg 甘草酸片可改善压力超负荷大鼠的心脏舒张功能。18β-GA 和雷诺嗪对降低心肌细胞游离钙有相似的作用。该研究表明，18β-GA 和甘草酸可改善 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期钠电流有关。
