Interventional Effects And Mechanisms Of Ginsenoside-Rb Group Monomers And Rd On The Myocardial Ischemia In Rats

Myocardial infarction (MI) is one of the major diseases contributing to global death and disabilities. MI is a kind of heart disease generally caused by myocardial ischemia, hypoxia and necrosis due to obstruction or stenosis lumen of coronary artery atherosclerosis and coronary artery spasm. Some exceptions are due to coronary artery congenital anomalies and coronary artery disease. Recently, the incidence of this ischemic heart disease shows an increasing trend year by year and seriously endangers people's health. Therefore, it is urgent and necessary for us to seek some effective treatments to conquer it. Ginseng is a well-known traditional Chinese medicine, which is mainly composed of ginsenosides, ginseng polysaccharides and a variety of active peptides. Large numbers of evidence indicates that ginseng can protect myocardium from ischemia injury through the mechanisms of stabilizing the cell membrane, anti-oxidation, anti-arrhythmic, anti-shock and so on.Objective:In this project, we used rat as our research model of acute myocardial ischemia. We aim to find out the effects and mechanisms of ginsenoside-Rb1, Rb2, Rb3 and Rd in the acute myocardial ischemia of rats through the observation of myocardial infarction area and three typical myocardial enzymes. Besides, we also investigated the expressions of proteins p-Akt, NF-κB(p-65), XIAP, Calpain-1, Caspase-12, Caspase-9 and Caspase-3, which have been reported to have close correlation with the myocardial ischemia injury. Our research will make theoretical preparations for the clinical application of Ginseng in curing the myocardial ischemia.Methods:Wistar rats were divided randomly into six groups: model, nitroglycerin (0.22mg·kg-1), Rb1 (20mg·kg-1), Rb2 (20mg·kg-1), Rb2 (20mg·kg-1) and Rd (20mg·kg-1). After anesthetized, the acute ischemia model was made by ligating the left anterior descending branch of coronary artery. Blood samples were taken for measurement. Rats were sacrificed 24h later after ligation. Drugs were administered for 7 consecutive days prior to the operation. The activities of serum creatine kinase(CK), lactate dehydrogenase(LDH)and aspartic transaminase(AST)were measured and myocardial infarction area was determined by using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Moreover, Immunohistochemistry staining was adopted to examine the expressions of myocardial p-Akt, NF-κB, XIAP, Calpain-1, Caspase-12, Caspase-9 and Caspase-3.Results:Compared with model, activities of CK, LDH and AST in serum were decreased to different extent and the infarct areas were reduced obviously in groups of ginsenoside-Rb1, Rb2, Rb3 and Rd (20 mg·kg-1 i.p.) in the acute myocardial ischemia of rats (P<0.05). As to the aspect of blood flow, the drug treatment groups can prevent of platelet aggregation and reduce the blood viscosity in contrast to model (P<0.05). HE result of model shows that majority of myocardial cells in the left ventricular anterior wall were seriously injured and went necrosis with interstitial myocardial edema and monocytes diffusion. In comparison, lesions of Rb1, Rb2, Rb3 and Rd groups were significantly reduced with slight edema, only a small number of monocytes and neutrophisl were visible under the light microscope. Ginsenoside-Rb1, Rb2 and Rd can up-regulate the expressions of myocardial p-AKT, NF-κB, XIAP while down-regulate the expressions of protein Caspase-3. It seems that ginsenoside- Rb3 doesn't have obvious influence on the above proteins. Ginsenoside-Rb1 can decrease the levels of Calpain-1 and Caspase-12. Caspase-9 was expressed less affected by Ginsenoside- Rb1 and Rd.Conclusion:Ginsenoside-Rb1, Rb2, Rb3 and Rd were found to relieve the myocardial ischemia injury in rats in different aspects. They can diminish the myocaridal infarct areas, reduce the serum myocardial enzymes and decrease the myocardial cells necrosis. Morever, Ginsenoside-Rb1, Rb2, Rb3 and Rd can prevent platelet from aggregation and reduce blood viscosity values. Certain key apoptosis-related proteins expressions were regulated as well. Specifically speaking, Ginsenoside- Rb group monomers and Rd can enhance the levels of p-AKT, NF-κB, XIAP and decrease expressions of Calpain-1, Caspase-12 and Caspase-9, which are the significant proteins in the apoptosis pathways.The results above indicate that Ginsenoside-Rb1, Rb2, Rb3 and Rd have interventional effects on the myocardial ischemia injury through the influence of several apoptosis pathways.