Effect Of Breviscapine On Cardioprotection And Its Mechanism

Ischemic heart disease (IHD) is a kind of severe cardiovascular disease, which mechanism is very complex and related to many systems of body. On cellular and molecular levels, the metachanism system of substance and energy of cardiomyocytes and gene expression pathway in cardiomyocytes would be changed by ischemia or/and hypoxia of heart, and these changes contribute to the process of ischemic injury of cardiac muscle as well. Drugs treatment is one of the most important therapeutic methods of ischemic heart diseases. There are many active substances with anti-myocardial ischemia physiological activity in nature products. So looking for the active substances with anti-myocardial ischemia physiological activity from nature products is important for exploitation of new drugs.Breviscapine is a flavonoid extracted from Erigeron briviscapus(vaniot). Hand.-Mazz., a popular Chinese herb medicine, which have many effects on brain ischemia , hemodynamics, microcirculation, and learning skill and have been applied broadly in clinic. But very little report is available regarding the cardioprotection of breviscapine, especially on cellular level. The purpose of this study is to investigate protective effects of breviscapine on acute myocardial infarction model induced by coronary ligation in vivo and cardiomyocytes damage model induced by hypoxia and reactive oxygen species (ROS) in vitro, and explore the protective mechanism in cellular and molecular levels.1. The effect of breviscapine on heart ischemia was studied on the acute myocardial infarction model induced by ligation of the left anterior descending coronary artery in dog heart in vivo. The total ST-segment elevation (∑ST) and the number of the leads (N-ST) on which the ST-segment elevation (>2 mv) on ECG, the infarct area ratio, the change of the serum LDH and CK were investigated on the acute myocardial infarction model. Additionally, the effect of breviscapine on myocardial oxygen consumption was detected in dog myocardium in vitro. The results demonstrate in an in vivo canine model of acute myocardial infarction that administration of breviscapine causes decrease of ST-segment elevation on ECG, reduction of myocardial infart size, decrease of serum LDH and CK concentration and reduction of myocardial oxygen consumption. Therefore, the results proved the anti-myocardial ischemia physiological activity of breviscapine.2. The effect of breviscapine on cardiomyocytes damage was studied on cardiomyocytes damage model induced by hypoxia and ROS (H2O2) of cultured neonatal rat cardiomyocytes in vitro. The LDH leakage was detected on cardiomyocytes subjected to hypoxia injury and the cellular metabolism and the activity of SOD was detected on cardiomyocytes subjected to ROS injury. The results showed that breviscapine could reduce the LDH leakage of cardiomyocytes induced by hypoxia injury and increase the cellular metabolism and the SOD activity of cardiomyocytes subjected to ROS injury. Therefore, the results prove that breviscapine can protect cardiomyocytes from damage directly.3. On cardiomyocytes damage model induced by hypoxia and ROS (H2O2) of cultured neonatal rat cardiomyocytes in vitro, the effect of breviscapine on apoptosis and necrosis was studied with the flow cytometry techniques as well as AnnexinV-FITC/PI stain techniques. There is no report to show that this sort of experiment has ever done elsewhere. Many studies confirmed that apoptosis of cardiomyocytes is one of important mechanisms of ischemic heart disease. Cardiomyocytes apoptosis is the primary approach of cardiomyocytes damage caused by acute myocardial infarction. And cardiomyocytes necrosis is the mean reason for cardiomyocytes lost in infartion area of heart which happens after apoptosis. The results of this study showed that breviscapine could reduce apoptosis and necrosis of cardiomyocytes induced by hypoxia and ROS. Therefore, the results suggested that reduction of apoptosis and necrosis of...