The Cardioprotective Potential And The Molecular Mechanisims Of Dendrobium Officinale Kimura Et Migo Against Myocardial Ischemia In Vitro And In Vivo

It was reported that there were 17.5 million people died from cardiovascular disease in 2012. Cardiovascular diseases（CVDs）, especially ischemic heart disease, are primary cause of disability and death worldwide. With the aging of population, the incidence of cardiovascular disease, such as coronary heart disease, is increasing year by year. CVDs is a serious threat to the people. Traditional Chinese medicine believed that thoracic obstruction was caused by blood stasis. Traditional Chinese medicine had extensive clinical experience in the treatment of thoracic obstruction. Compared with chemical synthetic drugs, traditional Chinese medicine had advantages in less toxicity, non-tolerance and long-term application. Therefore, the study of anti-ischemic drugs which is safer and more effective is necessary.It was described that Dendrobium had effects on tonifying five organs and the antiaggregation activity. The preliminary studies had shown that Dendrobium officinale had therapeutic effects on hypertension and atherosclerosis. So,we hypothesized that the water extract of Dendrobium officinale（DOE） might possess the cardioprotective effect against myocardial ischemia and we explored the mechanisms.The experiment included in vitro and in vivo experiments. In vitro experiments, H₂O₂ was used to induce oxidative stress injury. The experiment included five groups: control group, H₂O₂ model group, H₂O₂+DOE（0.1, 0.2, 0.4mg/mL）. MTT was used to measure the cell viability. The cell viability was 59.4±1.8% in H₂O₂- induced group and 69.7±1.8%, 77.5 ±1.3%, 83.7±1.6% in DOE（0.1, 0.2, 0.4mg/m L） group. Pre-exposure of DOE attenuated the cell viability against H₂O₂. DOE could significantly inhibit H₂O₂-induced apoptosis in AO staining. The levels of MDA, SOD, MMP and ROS were also determined. Results showed that DOE increased SOD and MMP levels, inhibited the generation of ROS and MDA concentration. The present study suggested the cytoprotective of DOE against H₂O₂-induced toxicity in H9C2. The result also demonstrated the antioxitive performance of DOE.In vivo experiment, mouse myocardial ischemia model was induced by ligation of the left anterior descending coronary artery（LAD）. Before operation, mice were given vehicles or DOE for 2 weeks. The experiment included five groups: control group, model group, LAD+DOE（75, 150, 300mg/kg）. After operation, ST elevation was then measured. To estimate the extent of myocardial damage, infarct size and histopathological examination were performed. The activities of cardiac marker enzymes（creatine kinase-MB, lactate dehydrogenase） and antioxidative indicators（malondialdehyde, superoxide dismutase） were further carried out to explore the underlying mechanisms. DOE decreased infarct size and reduced serum creatine kinase-MB, lactate dehydrogenase and malondialdehyde activities, and increased superoxide dismutase level. TUNEL assay was performed to measure the apoptosis of myocardial tissue. The apoptotic rate is 54.2±7.5% in model group and 42.5±12.4%, 37.3±1.6%, 18.2±4.5% in DOE group. DOE inhibited the apoptosis of myocardial tissue. According to the western blotting analysis, DOE conferred resistance to myocardial ischemia injury, thereby regulating the expression of Meis1. These results indicated that DOE had a potential cardioprotective effect against myocardial ischemia, which may be related with its antioxidative activity, inhibition of the cardiac cell apoptosis and the regulation of the expression of Meis1.The experiments in vitro and in vivo showed that Dendrobium officinale would be a potential candidate treatment in attenuation and prevention of myocardial ischemia in clinical usage. The mechanisms were possibly associated with the restoration of antioxidative activity, inhibition of apoptosis and up-regulation the expression of Meis1. This finding might be beneficial for patients suffered from myocardial ischemia, thus prompting to conduct further work to elucidate the precise molecular mechanism of DOE. Researchers had focused on traditional Chinese medicine in cardiovascular drug research. Traditional Chinese medicine had advantages on multi-target, multi-adjustable and prevention and treatment integrated. In contrast, Dendrobium officinale is one of traditional Chinese medicine. In recent years, it has been widely planted. It mainly consist of polysaccharide. It is important for prevention and treatment of myocardial ischemia to research traditional Chinese medicine with low toxicity and high yield.