The Effect Of The Combination Of Sal B And PNS On Rats With Myocardial Infarction And The Molecular Mechanism Of Limiting Myocardial Apoptosiss

Background and ObjectiveSalvia miltiorrhiza Bunge and Panax notoginseng are major ingredients of the Compund Danshen Formula. Previous researches have proved that there exists the best ratio when these two herbs are used in combination. Salvianolic acid B (Sal B) and panax notoginseng saponins (PNS) are major components isolated from them respectively. In order to search for the molecule mechanism of Sal B and PNS against myocardial infarctiom and elucidate the scientific connotation of compatibility in TCM formulas, we observed the effects of Sal B and PNS used alone and in combination on rats with acute myocardial infarction. MethodsWe produced myocardial infarction in anaesthetized rats by occluding the left descending coronary artery. Sham-operated rats served as controls. Rats were randomly divided into eight groups and treated with angiotensin converting enzyme inhibitor (ACEI) captopril, Sal B, PNS and the combination of Sal B and PNS. Control and model received saline only.1. In order to measure the infarcted area, we assayed the weight of the left ventricular and left ventricular infracted tissue. The plasma contention of Ang II was also assayed.2. We observed the effects of Sal B and PNS used alone and in combination on hemodynamic in rats.3 . We assayed the construction and function of left ventricular by using echocardiography.4. We observed gene expression changes in the areas near the infarcted tissue using the Affymetrix GeneChip Arrays.5. The number of apoptotic myocytes was determined using Annexin V-FITC/Pi by flow cytometry.6. By using real-time RT-PCR, we assayed the mRNA expression of myocardialapoptosis related genes. Results1. Sal B, PNS and the combination of Sal B and PNS can decrease the infarcted areas and the plasma content of Ang II compared with model. There was a trend that the effects of high dose group of the combination of Sal B and PNS were better than others.2. Sal B, PNS and the combination of Sal B and PNS can decrease the elevation of ST-segment. Sal B and PNS also can reduce the release of LDH, decrease the left ventricular diastolic pressure (LVDP), and increase +dp/dtmax and -dp/dtmax. There was a trend that the effects of Sal B and PNS used in combination were better than alone.3. Sal B, PNS and the combination of Sal B and PNS can decrease LVDs, LVPWs, LVESV and increase EF and FS. There was a trend that the effects of middle dose group of the combination of Sal B and PNS were better than others.4. Of the genes on the arrays, there were 22% genes in the model group changed in expression level relative to the control, 11% genes were differentially expressed in higher level and another 11% genes were in lower level. The genes displayed a minimum of twofold change in expression level include clotting system regulators, left ventricular remodeling genes, immune response-related genes, energy metabolism regulators, inflammatory factors, signal transducing molecules.There were 5.7% genes in Sal B group changed and 0.3% displayed a minimum of twofold change in expression level over the model group. There were 5.7% genes in PNS group changed and 0.8% displayed a minimum of twofold change in expression level over the model group. There were 14% genes changed in Sal B and PNS group and 3% displayed a minimum of twofold change, in expression level over the model group. The genes differently expressed in Sal B and PNS group were more than the groups used alone.5. All the treated groups can limit the percent of myocardial apoptosis and the effect of the combination is the most significant.