2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38799Endothelin type A receptor antagonist has been shown to improve sleep-related hypertension and cardiovascular injury in 2008 Am J Physiol Heart Circ Physiol (Allahdadi et al., 2008). Cardiac apoptosis have two major apoptotic pathways, Fas death receptor-dependent and mitochondria-dependent apoptotic pathways. However, Effects of endothelin type A receptor antagonist and exercise therapy on sleep apnea-induced Cardiac apotosis is still totally unknown. The first year: To further clarify the effects of endothelin Type A receptor antagonist pathways of cardiac apoptosis in sleep apnea. There are four group [G1: normoxia Control (n=20); G2: Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G3: Endothelin Type A receptor antagonist BQ-123 (100 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G4: Endothelin Type A receptor antagonist BQ-123 (1000 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20)]. Blood pressure, Type I cardiac apoptosis (Fas ligand, Fas Death-receptor, caspase 8, and caspase 3) and Type II cardiac apoptosis (Bcl2 family proteins-Bcl2, BNIP3, Bad, cytochrome c release,caspase 9, and caspase 3), and PI3K-Akt survival signaling pathways in there four groups will be measured by tail cuff measurement, multiple experimental methods related cardiac apoptosis such as cross section, H&E staining, TUNEL assay, western blotting, and RT-PCR. The second year: To determine the effects of exercise therapy on cardiac apoptosis in Sleep apnea. There are three group [G1: normoxia Control (n=20); G2: Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G3: Swimming training (Pre-conditioning 14 days+ conditioning 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20)]. Blood pressure, cardiac Fas and mitochondria dependent apoptotic and PI3K-Akt survival signaling pathways will be measured by multiple experimental methology such as cross section, hematoxylin and eosin staining, TUNEL assay, western blotting, and RT-PCR. The third year: To determine the effects of exercise training on cardiac apoptosis in type II DM. There are five group [G1: normoxia Control (n=20); G2: Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G3: Endothelin Type A receptor antagonist BQ-123 (100 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G4: Swimming training (Pre-conditioning 14 days+ conditioning 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G5: Swimming training (Pre-conditioning 14 days+ conditioning 14 days) +Endothelin Type A receptor antagonist BQ-123 (100 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20)]。Blood pressure, cardiac Fas and mitochondria dependent apoptotic and PI3K-Akt survival signaling pathways will be measured by metabolic treadmill, tail cuff measurement, and multiple experiments related cardiacapoptosis such as cross section, H&E staining, TUNEL assay, western blotting, and RT-PCR.2008 年在Am J Physiol Heart Circ Physiol 期刊提出Endothelin type A receptor antagonist 改善睡眠呼吸終止症(夜間漸歇性缺氧)的老鼠的血壓和心血 管的傷害(Allahdadi et al., 2008)。心臟細胞凋亡途徑可分為Fas death receptor-及 mitochondria- dependent 兩種主要途徑，然而是否內皮素A 型受體拮抗劑或運動 治療對睡眠呼吸終止症(夜間漸歇性缺氧)中心臟細胞Fas& Mitochondrial 凋亡途 徑的療效，至今仍未知。 第一年計劃: 為了探討內皮素A 型受體拮抗劑對睡眠呼吸終止症(夜間漸歇 性缺氧)中心臟細胞Fas& Mitochondrial 凋亡和PI3K-Akt 存活途徑途徑的影響。 實驗共分成four group [G1: normoxia Control (n=20); G2: Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G3: Endothelin Type A receptor antagonist BQ-123 (100 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G4: Endothelin Type A receptor antagonist BQ-123 (1000 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20)] 進行血壓、多重凋亡相關實驗 法例如組織切片、TUNEL assay、western blotting、RT-PCR 等實驗方法來加以分 析並加以探討其心肌細胞凋亡的現象，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)和PI3K-Akt 等訊息傳遞路徑。 第二年計劃:為了探討運動治療對睡眠呼吸終止症(夜間漸歇性缺氧)對於心 臟細胞抗凋亡和PI3K-Akt 存活途徑的療效，因此本實驗第二年計劃將three group [G1: normoxia Control (n=20); G2: Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G3: Swimming training (Pre-conditioning 14 days+ conditioning 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20)] 進行血壓、多重凋亡相關實驗法例如組織切片、western blotting、 TUNEL assay, RT-PCR 等實驗方法來加以分析並加以探討其心肌細胞凋亡的現 象，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) 和 PI3K-Akt 等訊息傳遞路徑。 第三年計劃:為了探討內皮素A 型受體拮抗劑配合運動治療是否加乘對睡眠 呼吸終止症(夜間漸歇性缺氧)對於心臟細胞抗凋亡和PI3K-Akt 存活途徑之療 效，因此本實驗第三年計劃將將分五組[G1: normoxia Control (n=20); G2: Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G3: Endothelin Type A receptor antagonist BQ-123 (100 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G4: Swimming training (Pre-conditioning 14 days+ conditioning 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20); G5: Swimming training (Pre-conditioning 14 days+ conditioning 14 days) +Endothelin Type A receptor antagonist BQ-123 (100 nmol.kg(-1).day(-1) sc for 14 days) + Intermittent hypoxia (2 min N2 + 2min normoxia, 8 hour, 2 weeks, n=20)]。加以探討其血壓、Fas 和 mitochondria-dependent 心肌細胞凋亡和PI3K-Akt 存活途徑的現象。Project