| 摘要: | SIRT1,是一個卡路里限制導至抗老化主要調制機制，對治療老化疾病是一種 新且有效的治療方法例如第二類型糖尿病。心臟細胞凋亡途徑可分為Fas death receptor-及mitochondria- dependent 兩種主要途徑，心臟細胞凋亡途徑會隨著各 種病理機制或外在的壓力如高血壓、肥胖、缺氧、自由基等促進凋亡途徑的活化。 糖尿病是常見的慢性疾病，糖尿病是造成心臟病的主要危險因子為眾所周知的 事。從本實驗室初步重要的發現糖尿病誘發鼠發現心臟細胞凋亡的現象，然而 SIRT1 activators 配合運動治療對第二型糖尿病抗老化延壽(SirT, PGC1- α, FoxO, and PBEF)和抗心臟(Fas/Mitochondria)細胞凋亡的療效仍未知。 計劃方法: 為了探討SIRT1 activators 配合運動治療對第二型糖尿病心臟細 胞的凋亡。實驗共分成five groups [Group1: ControlWistar (n=20、16 週齡); Group 2: Type-II-DM (n=20、16 週齡雄性Goto-Kakizaki (Type 2) diabetic rats); Group 3: SIRT1 activators (Resveratrol, 10mg/kg per day i.p. for 12 weeks) in Type-II-DM (16 週齡雄性Goto-Kakizaki (Type 2) diabetic rats n=20); Group 4: Swimming training (1hr/per day, 3 days/week for 12 weeks) in Type-II-DM (16 週齡雄性Goto-Kakizaki (Type 2) diabetic rats n=20); Group 5: SIRT1 activators (Resveratrol, 10mg/kg per day i.p. for 12 weeks) + swimming training (1hr/per day, 3 days/week for 12 weeks) in Type-II-DM (16 週齡雄性Goto-Kakizaki (Type 2) diabetic rats n=20)]；進行血糖 測試、血壓測試、多重凋亡相關實驗法例如組織切片、western blotting、RT-PCR、 TUNEL asssay 等實驗方法來加以分析並加以探討其心肌細胞抗老化和抗凋亡的 現象，抗老化(SirT, PGC1-α, FoxO, and PBEF)， Fas death receptor-dependent 心肌細胞凋亡(Fas ligand, Fas Death-receptor, caspase 8, and caspase 3)和 mitochondria-dependent 心肌細胞凋亡(Bcl2 family proteins-Bcl2, BNIP3, Bad, cytochrome c release, caspase 9 and caspase 3)等訊息傳遞路徑。 此研究進一步系統性了解SIRT1 activators 配合運動治療對第二型糖尿病對於 心臟細胞FAS 和MITOCHONDRIA 凋亡的影響，這些突破性的研究將能提供有價值 的醫療資訊關於第二型糖尿病引起的心肌凋亡，將有助於未來發展出或預防或第二 型糖尿病引起心血管疾病的預防及治療的方法。
SIRT1, increases longevity and is a new therapeutic approach to treat aging, such as diabetes. Cardiac apoptosis have two major apoptotic pathways, Fas death receptor-dependent and mitochondria-dependent apoptotic pathways. Cardiac apoptotic pathways can be activated by various pathologic and stress condition such as hypertension, obesity, hypoxia, free radicals. Diabetes (DM) is a very common chronic diseases and it is well known that DM is major risk factor of cardiovascular diseases. However, effect of SIRT1 activators and exercise therapy on Cardiac apotosis in Type II diabetes rats is still totally unknown. To clarify the pathways of cardiac apoptosis in type II DM. There are five groups [Group1: Control Wistar (n=20、16 週齡); Group 2: Type-II-DM (n=20、16 週齡雄性Goto-Kakizaki (Type 2) diabetic rats); Group 3: SIRT1 activators (Resveratrol, 10mg/kg per day i.p. for 12 weeks) in Type-II-DM (16 week old male Goto-Kakizaki (Type 2) diabetic rats n=20); Group 4: Swimming training (1hr/per day, 3 days/week for 12 weeks) in Type-II-DM (16 week old male Goto-Kakizaki (Type 2) diabetic rats n=20); Group 5: SIRT1 activators (Resveratrol, 10mg/kg per day i.p. for 12 weeks) + swimming training (1hr/per day, 3 days/week for 12 weeks) in Type-II-DM (16 week old male Goto-Kakizaki (Type 2) diabetic rats n=20)]. Glucose testing, blood pressure tests, anti-aging (SirT, FoxO, and PBEF), FAS death receptor dependent cardiac apoptosis (Fas ligand, Fas Death-receptor, caspase 8, and caspase 3) and Mitochondria dependent cardiac apoptosis (Bcl2 family proteins-Bcl2, BNIP3, Bad, cytochrome c release,caspase 9 and caspase 3) signaling pathways in there groups will be measured by Accu Soft (Hoffmann-La Roche) test strips, tail cuff measurement, multiple experimental methods related cardiac apoptosis such as cross section, H&E staining, western blotting, RT-PCR, and TUNEL. This research can understood that effect of SIRT1 activators and exercise therapy on cardiac FAS and MITOCHONDRIA dependent apoptotic pathways in the type II diabetes. The unprecedented research will be able to provide the valuable medical information about cardiac apoptosis in Type II diabetes. The current study will be helpful in the future develops either the prevention of cardiovascular diseases in diabetes. |
