1.Reveal the signaling pathways of Dioscorea extract suppress cardiomyocytes apoptosis and provide protective effects in ovariectomized rats2.Investigation the effect of exercise on cardiomyocytes apoptosis in hereditary obese Zucker Rats

• Main Authors: Ann-Chi, 林安琪
• Other Authors: 黃志揚
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/34143747757826081359

碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 94 === 1.Reveal the signaling pathways of Dioscorea extract suppress cardiomyocytes apoptosis and provide protective effects in ovariectomized rats World Health Organization indicat that Cardiovascular disease is the leading cause of mortality. The phenomenon also in our country. The cardiovascular disease is significantly lower in women than in men until menopause, after which the cardiovascular risk of women accelerates to equal that of men. Therefore this observation suggests a possibility that female sex hormones, such as estrogen, may have a favorable cardiovascular role. On the other hand, in order to diminish the syndrome of menopausal, most of women will use the Hormone Replacement Therapy(HRT). But one thing that let us attention, the side effect of HRT：Breast cancer. The structure of compound that called Diosgenin which included in Dioscorea spp. was similar to estrogen. We wish to substitute HRT and explore how mechanism of protect to cardiomyocytes？ Ovariectomized rats, aminal models of the status of postmenopausal women, were feed with various dose of Dioscorea spp., for a month, rats hearts were isolated to analysis effects of apoptotic and survival mechanism in cardiomyocytes. First we use H&E stain and Trichrome Masson stain to prove that ovariectomized injury in cardiomyocytes could be to decrease by Dioscorea spp. Analysis to TUNEL assay, we found that apoptosis in cardiomyocytes were suppressed by Dioscorea spp. Go on to analysis with western blot and RT-PCR, we demonstration that apoptosis in cardiomyocytes were induced by death receptor dependent pathway and mitochondria dependent pathway. We also found ERK and P38 were influence by ovariectomized injury which could induced by Dioscorea spp. Finally, we confirm Dioscorea spp. was similar to estrogen could active ERα and PI3K/Akt pathway, that could protect to cardiomyocytes. In our study, that prove Dioscorea spp. could protect to cardiomyocytes. Maybe can application in clinical and to substitute HRT in future. 2.Investigation the effect of exercise on cardiomyocytes apoptosis in hereditary obese Zucker Rats The life style was change in recent years, there were more and more persons face of obesity. The body image was change and the risk of chronic disease were increase in obesity persons, such as diabetes mellitus、hypertension and heart disease etc. To solve that problem of obesity are food control and exercise. Indication of many study, exercise could activate AMP-Activated Protein Kinase；AMPK. AMPK was an important regulator of energy. When the ratio of AMP：ATP was drop, AMPK were activated, that the carbohydrate and fat were to decomposed. AMPK activates the catabolic pathway and inhibits the anabolic pathway. But who could activates AMPK？ We don’t understand. Up to now we know that AMPK could activated by exercise、ischemia and lack of energy. Therefore we use Zucker Rats that have inborn of hereditary obese, mimic the model of obesity in human. Exercise training for one hour in everyday continues eight weeks. After exercise training, Zucker Rats were scarificed then isolated the heart to study. After exercise training, no matter lean or obesity Zucker Rats, apoptosis in cardiomyocytes was vary critical. At the same time, we also analysis Akt that the upstream of AMPK, which was increase. We also found GPCR could induced by exercise training, then activates PKCδ to protect the heart. Stress of exercise training to cardiomyocytes, except activates apoptosis pathway also could induces that protective pathway to heart. In addition apoptosis were activated, the body weight of Zucker Rats were got lost by exercise training.