17β-雌二醇心血管作用及其机制的研究

作     者：刘文华 

作者单位：南京医科大学 

学位级别：硕士

导师姓名：张治芬

授予年度：2016年

学科分类：1002[医学-临床医学] 100211[医学-妇产科学] 10[医学] 

主      题：17β-estradiol SIRT1 AMPK MCP-1 RhoA Cardiovascular protective effects 

摘      要：Backgroud:Estrogen has extensive biological effect including against hypertension, atherosclerosis, lipid peroxidation and vascular injury, which play a pivotal role in cardiovascular protection. Vascular endothelial disfunction and myocardial metabolic disorder have been implicated in the pathogenesis of cardiovascular disease(CVD). Menopause means ovarian function failure and downstream estrogen levels. Premenopausal women are less risk of cardiovascular disease than men, the risk increase after menopause, similar to male. The International Menopause Society (IMS) in 2013 pointed out that perimenopausal and postmenopausal women with utilization of menopause hormone therapy (MHT) early can improve vessel function, lower cholesterol levels, regulate glycometabolism and blood pressure, which has potential cardiovascular protective effect, but the specific mechanism is unclear. Chronic inflammation and oxidative stress, is a central pathology physiology of the cardiovascular disease. Monocyte chemotactic factor 1 (MCP-1) inducts, regulates other formation and release of inflammatory factor, the formation of cascade, mediating inflammation, therefore it is considered to be the start of the inflammatory response factor. Induction of MCP-1, monocyte/macrophage activation and the accumulation of the subcutaneous is a key factor of atherosclerosis. RhoA belongs to Rho guanosine triphosphatase family, participating in maintaining vascular endothelium and the myocardial cytoskeleton structure, which plays an important role in regulation of cell migration. In recent years, studies have shown that SIRT1 can inhibit oxidative stress, inflammation, apoptosis, promote glucolipid metabolism, cell DNA damage repair, atherosclerosis, myocardial ischemia, myocardial hypertrophy and pathological processes of cardiovascular disease. AMP activated protein kinase (AMPK) is a cellular energy switch, adjust the AMP/ATP ratio, promote the mitochondrial oxidative metabolism of the generation