Study On The Protection Mechanism Of Ginsenoside Re To Cardiocyte Apoptosis Induced By Elevated Catecholamine In Rats

Objective: To study the protection mechanism of Ginsenoside Re to cardiocyte apoptosis induced by elevated Catecholamine in rats.Methods: The experiment was divided into two parts. The first part was the therapeutic action of GSRe on cadiocyte apoptosis induced by the elevated catecholamine and the second part was the precautionary action of GSRe in the same situation. In the fisrt part, there were three groups: control groups, Isoproterenol group and GSRe treatment group. In the second part, there were also three groups: control groups, Isoproterenol group and GSRe Prevention group. Each group had six rats. Apoptosis and ventricular arrhythmia was induced by peritoneal injection of isoproterenol(15mg/kg) for three days. In the GSRe Treatment group, GSRe (20mg/kg) was injected through the caudal vein 20 minutes after the isoproterenol. And the GSRe Prevention group, 20 minutes earlier. To record the change of ECG and the heart rate of the first,third,fifth,seventh and tenth minute of each group. Afer 72 hours of the first injection of isoproterenol, the rats were executed and the myocardium from left ventricle were gotten to check. The histopathological change of myocardium was investigated by HE staining, the myocardial cell apoptosis were observed TUNEL method and the ultrastructure of myocardial cell examined by electron microscope. The expression of Fas and Bcl-2 gene proteins were studied by immunohistochemical staining. Through these methods, we studied the deleterious effect of elevated Catecholamine and the protective effect of ginsenoside Re.Results: 1. By peritoneal injection of 15mg/kg, isoproterenol could trigger ventricular arrhythmia. Compared with the control group, the HR of the first,third,fifth,seventh and tenth minute in ISO group showed significant difference.2. By peritoneal injection of 15mg/kg for three days, isoproterenol could not induced myocardium necrosis but apoptosis in rat. The optical microscope checked result showed that there were only denaturation in myocardium. The characteristic changes of cell apoptosis were observed under electron microscope, such as volume smaller,the change of ceil nucleus and chromatin collection. The index ofapoptosis cell was(49.73±6.82)(%), compared with(9.70±3.34)(%)in control group (P＜0.01).And the difference was significant in the expression of Fas and Bcl-2 gene proteins, (59.40±6.50)(%) and(41.20±8.21)% respectively, compared with (14.43±5.56)(%) and (17.80±7.83)(%) (P＜0.01, P＜0.01).3. Injection through the caudal vein of GSRe 20mg/kg could treat the triggered ventricular arrhythmia rats in vivo, and it could slow down the heart rate. The difference was significant between the ISO group and the GSRe treatment group (P＜0.01). Under electron microscope, most cell nucleus were normal and the nucleolus could be seen. The number of apoptosis cell in the GSRe treatment group is (27.30±4.16)(%), compared with (49.73±6.83)(%) in the ISO group (P＜0.01). And the difference was significant in the expression of Fas and Bcl-2 gene proteins, (40.77±8.34)(%) and (49.67±7.35)(%) respectively, compared with (59.40±6.50)(%) and (41.20±8.21)(%) in ISO group (P＜0.01, P＜0.01)4. Prophylacticn injection through the caudal vein of GSRe 20mg/kg had antagonism to the triggered ventricular arrhythmia and the heart rate increased induced by ISO. The difference was significant between the ISO group and the GSRe prevention group (P＜0.01). There was no characteristic changes of cell apoptosis observed under electron microscope, most structure of cell nucleus were normal. The number of apoptosis cell in the GSRe prevention group is (29.47±4.67)(%), compared with (49.73±6.83)(%) in the ISO group (P＜0.01). And the difference was significant in the expression of Fas and Bcl-2 gene proteins, (38.63±6.58)(%)and (50.63±7.78)(%) respectively ,compared with (59.40±6.50)(%) and (41.20±8.21)(%) in ISO group (P＜0.01, P＜0.01).Conclusion: 1. ISO could induce triggered ventricular arrhythmia.2. ISO could induce cardiocyte apoptosis, and this before the happening of cardiocyte necrosis. 3. GSRe could prevent and stop the triggered ventricular arrhythmia induced by elevated catecholamine and it can improve the haemodynamics condition at the same time.4. GSRe could significantly inhibit cardiocyte apoptosis induced by elevated catecholamine. And this is finished through down-regulate the Fas gene protein expression and up-regulate the Bcl-2 gene protein expression.5. As a antiarrhythmia and cardiocyte protection medicine, GSRe could use to treat triggered ventricular arrhythmia and cardiocytel apoptosis induced by elevated catecholamine and to protect heart under this condition.