Myocardial Ischemia Protection Of Glycyrrhizic Acid Based On Calcium Homeostasis And Its Mechanism

Licorice is a common Chinese medicine and the efficacy of licorice includes tonifying spleen qi,relieving pain and clearing away heat and toxic mererials.Licorice is used to treat palpitation and intermittent pulse because it is sweet and enters the heart meridian.Glycyrrhizic acid is one of the main active ingredients of licorice.The potential protective mechanism of glycyrrhizic acid on myocardial ischemia,especially the electrophysiological mechanism of calcium ions(Ca²⁺),has not been systematically investigated.Ischemic cardiomyopathy is a clinical condition in which the coronary artery blood flow is decreased,leading to insufficient supply of myocardial oxygen and other substances and decreased clearance of metabolites due to various reasons.Myocardial ischemia can cause a large amount of extracellular Ca²⁺to enter the cell by L-type Ca²⁺channel（LTCCs）,increasing intracellular Ca²⁺concentration and causing myocardial cell damage.Objective:To investigate the effect of gibberellin on acute myocardial ischemia in rats and its mechanism.Methods:On the one hand,the effects of GA on acute myocardial ischemia induced by isoproterenol（ISO）were studied by colorimetry,histopathology and electrocardiogram.On the other hand,L-type calcium channels current(I_Ca-L),cell contraction and intracellular Ca²⁺transient changes caused by GA were detected through whole-cell patch clamp technology,and myocyte calcium and contractility system（Ion Optix）.Results:1 Effect of GA on myocardial ischemia in ratsGA reduced the ST-segment elevation,decreased the heart rate,prevented ISO-induced QT-interval shortening,and decreased the activity of creatine kinase（CK）and lactate dehydrogenase（LDH）in serum of rats（P<0.01）.GA improved ISO-induced morphological pathologies.2 Effect of GA on I_Ca-LGA blocked I_Ca-L in a dose-dependent manner.The peak of I_Ca-L was progressively changed by the gradient concentrations of 10,30,100,300,and1000μg/m L of GA（P<0.01）.However,the effect of 1 and 3μg/m L GA were not statistically significant（P>0.05）.GA did not affect the dynamical properties of the Ca²⁺channel（P>0.05）.3 Effect of GA on cell contractionGA reversibly reduced the amplitude of cell contraction in a dose-dependent manner,prolonged the peak time and slowed down its deflection and recovery（P<0.05 or P<0.01）.4 Effect of GA on intracellular Ca²⁺transientGA reversibly reduced the amplitude of intracellular Ca²⁺transient in a dose-dependent manner,prolonged the peak time and slowed down its deflection and recovery（P<0.05 or P<0.01）.Conclusions:GA improves ISO-induced acute myocardial ischemia by inhibiting LTCCs,cell contraction,and intracellular Ca²⁺transients.