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  • 學位論文

第一部分 龍眼花萃取物對果糖餵養大鼠抗心臟凋亡分子機轉之探討 第二部分 Diosgenin對D-半乳糖誘導老化大鼠心臟凋亡和纖維化之探討

PartⅠ. Anti-apoptotic Effects of Longan Flower Extracts on Fructose-fed Rats Hearts.PartⅡ. Effects of diosgenin on cardiac apoptosis and fibrosis in D-galactose-induced aging rats.

指導教授 : 張筱筠 黃志揚 李信達
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摘要


第一部分 隨著國人代謝症候群發生機率的增加,並且發現代謝症候群是造成心血管疾病一個主要的危險因素。許多研究中認為代謝症候群,如肥胖、糖尿病和高血壓引起的心臟病變和心肌細胞凋亡有關,但確切相關路徑的研究探討卻是非常有限。本篇實驗將探討龍眼花萃取物對高果糖引起的代謝症候群,其心臟相關訊息傳遞路徑的影響。本研究利用Sprague-Dawley雄性大鼠,隨機分為五組:對照組(C)每日灌食去離子水並給予標準飼料;高果糖組(HF)每日灌食去離子水並給予高果糖飼料;龍眼花水萃物組(LFWE)每日灌食龍眼花水萃物250 mg/kg並給予高果糖飼料;龍眼花水萃物乙酸乙酯區分層組(LFEA)每日灌食乙酸乙酯區分層36.3 mg/kg並給予高果糖飼料;龍眼花水萃物水區分層組(LFW)每日灌食水區分層147.5 mg/kg並給予高果糖飼料。經過16週後,利用H&E stain、TUNEL assay和western blotting等實驗來觀察心肌細胞組織間和蛋白質間的變化。在高果糖組(HF)中,心肌細胞凋亡路徑的蛋白質表現量和對照組(C)相比有顯著的上升。而灌食龍眼花萃取物後的組別(LFWE, LFEA and LFW),相較於高果糖組(HF),凋亡相關路徑蛋白質表現量皆明顯下降。在survival訊息傳遞路徑中蛋白質的表現量,高果糖組(HF)明顯的比對照組(C)低。而灌食龍眼花萃取物後,蛋白的表現量皆有明顯的上升。總和以上結果, 在果糖餵養大鼠模型中,龍眼花萃取物可以抑制心肌細胞凋亡相關蛋白質的表現,並促進存活路徑的相關蛋白質表現量,保護心肌細胞免於走向細胞凋亡的途徑。因此本篇實驗發現龍眼花萃取物可提供代謝症候群病人一個有效預防心臟方面併發症的發生。 第二部分 在全球化社會年齡老化的現在,急需相當程度的了解老化影響著各器官的成因。許多研究中認為老化引起的心臟病變與心肌細胞的凋亡和纖維化有關,但確切相關路徑的研究探討卻是非常有限。本篇實驗將探討Diosgenin對D-半乳糖誘導的老化大鼠,其心臟相關訊息傳遞路徑的影響。本研究利用Wistar雄性大鼠,隨機分為對照組(S0)及老化組,老化組透過D-半乳糖誘導老化,再分別每天每公斤體重餵食0,10,50mg的Diosgenin (D0, DD10 and DD50)。經過8週後,利用H&E stain、TUNEL assay和western blotting等實驗來觀察心肌細胞組織間和蛋白質間的變化。在老化組(D0)中,心肌細胞凋亡路徑的蛋白質表現量和對照組(S0)相比有顯著的上升。而餵食Diosgenin後的組別(DD10 and DD50),相較於老化組(D0),凋亡相關路徑蛋白表現量皆明顯下降。在survival訊息傳遞路徑中蛋白質的表現量,老化組(D0)明顯的比對照組(S0)低。而餵食Diosgenin後,蛋白的表現量皆有明顯的上升。而在纖維化訊息傳遞路徑中蛋白質的表現量,老化組(D0)明顯的比對照組(S0)高。餵食Diosgenin後,蛋白的表現量皆有明顯的下降。總和以上結果,在D-半乳糖誘導的老化大鼠模型中,Diosgenin可以抑制心肌細胞凋亡和纖維化相關蛋白的表現,並促進survival的相關蛋白表現量,保護心肌細胞免於走向細胞凋亡的途徑。因此本篇實驗發現Diosgenin可提供老化相關疾病一個有效預防心臟方面併發症的發生。

關鍵字

高果糖 龍眼花 老化 D-半乳糖 細胞凋亡

並列摘要


Part I. The metabolic syndrome is a major risk factor for cardiovascular diseases and also raised the mortality. Cardiac apoptosis was found in metabolic syndrome such as obesity, diabetes, and hypertension. Very limited information regarding the effects of the supplementation of longan flower extracts in a fructose-fed rat model with metabolic syndrome. Male Sprague-Dawley rats were divided into five groups fed with standard Purina chow (Control group, C), high fructose diet (HF), high fructose diet plus longan flower water extract 250 mg/kg per day by gavage (LFWE), high fructose diet plus longan flower ethyl acetate fraction 36.3 mg/kg per day by gavage (LFEA), high fructose diet plus longan flower water fraction 147.5 mg/kg per day by gavage (LFW). After 16 weeks, hearts were measured by H&E stain, TUNEL assay and western blotting. Protein levels of Fas-dependent and mitochondria dependent apoptotic pathway, such as Fas, FADD, Bak, Cytochrome c, activated caspase-9 and activated caspase-3 were increased in HF group compared with C group, whereas those were decreased in LFWE, LFEA and LFW groups compared with HF group; and survival related proteins (IGF1-receptor, p-Akt, p-Bad, Bcl-2, Bcl-xL) were decreased in HF group compared with C group, whereas those were increased in LFWE, LFEA and LFW groups compared with HF group. Longan flower treatment might suppress cardiac apoptotic pathways and elevated cardiac survival pathway in fructose-fed rat model. The findings suggest that longan flower may be one of the possible therapeutic agents for preventing cardiac apoptosis in metabolic syndrome. Part II. Cardiac apoptosis and fibrosis was found in aging-related diseases. Very limited information regarding the effects of the supplementation of Diosgenin in a D-galactose-induced aging model. Male Wistar rats were divided into Control group (S0), aging group (D0), and D0 groups with 10mg/kg and 50mg/kg diosgenin spp.daily (DD10 and DD50). After 8 weeks, hearts were measured by H&E stain, TUNEL assay and western blotting. Protein levels of Fas-dependent and mitochondria dependent apoptotic pathway, were increased in D0 group compared with S0 group, whereas those were decreased in DD10 and DD50 groups compared with D0 group; and survival related proteins, were decreased in D0 group compared with S0 group, whereas those were increased in DD10 and DD50 groups compared with D0 group. Fibrosis related proteins, were increased in D0 group compared with S0 group, whereas those were decreased in DD10 and DD50 groups compared with D0 group. Diosgenin treatment might suppress cardiac apoptotic and fibrosis pathways and elevated cardiac survival pathway in D-galactose-induced aging model. The findings suggest that Diosgenin may be one of the possible therapeutic agents for preventing cardiac apoptosis in aging-related diseases.

並列關鍵字

high fructose longan flower aging D-galactose apoptosis

參考文獻


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