運動訓練對卵巢切除之大鼠心臟凋亡以及抗凋亡的影響

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Title:	運動訓練對卵巢切除之大鼠心臟凋亡以及抗凋亡的影響 Effect of exercise training on cardiac apoptosis and survival pathways in ovariectomized rats
Authors:	許智超;Chih-Chao Hsu
Contributors:	健康照護學院物理治療學系復健科學碩士班
Keywords:	心臟;卵巢切除;細胞凋亡;停經;heart;TNF-α;caspases;cell death;Ovariectomy
Date:	2010
Issue Date:	2010-09-29 12:08:47 (UTC+8)
Abstract:	研究資料顯示停經或卵巢切除後的婦女大幅提高了心臟疾病的風險。過去研究發現在卵巢切除的大鼠身上有心肌細胞凋亡的現象，然而對於停經或是卵巢切除後的女性運動對心肌細胞凋亡的影響方面的研究並不多。本篇的目的便在研究雙側卵巢切除後的大鼠經由運動訓練後對其Fas蛋白和粒線體依賴性心臟細胞凋亡以及存活和抗凋亡途徑的影響。實驗使用三十三隻大鼠，其中十一隻手術過程中不切除卵巢作為對照組，另外二十二隻卵巢切除大鼠中再隨機挑選十一隻於休息一周後開始進行十周的運動訓練。在訓練完成後將三十三隻大鼠犧牲取出心臟並測量heart index、hematoxylin-eosin staining、Western Blotting 以及 positive TUNEL assays。實驗結果卵巢切除組大鼠在心臟重、不正常的心肌組織、Fas以及粒線體依賴性心臟細胞凋亡途徑表現蛋白以及TUNEL陽性細胞，相較於對照組都有明顯的增加；而這些在運動組相較於雙側卵巢切除組則有明顯的下降。藉由本實驗證明了運動可以抑制或是預防卵巢切除所導致的Fas蛋白以及粒線體依賴性心臟細胞凋亡，並增進存活途徑的保護作用。由於雌激素與其替代品的補充治療有提高乳癌發生的風險，因此這項發現在停經或是卵巢切除後的婦女藉由運動預防心血管疾病上提供了一個新的治療效果。 Background. Cardiac apoptosis were found in ovariectomized rats but very limited information regarding the effects of exercise training on cardiac apoptosis in menopausal or bilateral oophorectomied women was available. The purpose of this study was to evaluate the effects of exercise training on cardiac Fas and mitochondria dependent apoptotic pathways and cardiac survival pathways in ovariectomized rats. Methods. Eleven sham-operated rats(Sham) and eleven ovariectomized rats(OVX) at 14 weeks of age were served as negative and positive control. Eleven ovariectomized rats underwent treadmill running exercise 1 hour daily for 10 weeks(OVX-EX). After exercise training or sedentary status, the excised hearts were measured by heart index, hematoxylin-eosin staining, Western Blotting and positive TUNEL assays. Results. The whole heart weight, the left ventricular weight, the ratios of whole heart weight to tibia length, and the ratios of left ventricle to tibia length were significantly increased in OVX relative to Sham. Abnormal myocardial architecture and more cardiac TUNEL-positive apoptotic cells were observed in OVX, but not in Sham. Cardiac Fas ligand, Fas death receptors, Fas-associated death domain (FADD), t-Bid, Bad, Bak, Bax, activated caspase 8, activated caspase 9, and activated caspase 3 in OVX were significantly increased, compared to Sham. OVX-induced protein levels of TNF-alpha, Fas ligand, Fas death receptors, FADD, activated caspase 8, and activated caspase 3 (Fas pathways) became lower in OVX-EX. OVX-induced protein levels of t-Bid, Bad, Bax, Bak, activated caspase 9, and activated caspase 3 (mitochondria pathway) became lower in OVX-EX. Furthermore Cardiac phosphorylated PI3K, phosphorylated AKT, phosphorylated p38, Bcl2 and phosphorylated Bad were significanly increased in OVX-EX, compared to OVX. Conclusions. Exercise training suppressed ovariectomy-induced cardiac Fas and mitochondria dependent apoptotic pathways, and furthermore it increase cardiac survival pathways in ovariectomized rat models. The findings may provide one of new therapeutic effect of exercise training on preventing cardiac apoptosis in iii menopausal or bilateral oophorectomied women.
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