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  • 學位論文

原兒茶酸對高血壓性心臟抗凋亡與促進存活的功效

Anti-apoptotic and Pro-survival Effect of Protocatechuic Acid on Hypertensive Hearts‏

指導教授 : 黃志揚
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摘要


高血壓是盛行率很高的疾病,為腦血管疾病、心血管疾病之最主要危險因子,高血壓初期並沒有症狀,需經年累月才會對器官造成傷害,亦號稱無聲的疾病殺手。許多研究中認為高血壓引起的心臟病變和心肌細胞的凋亡有關,但切確相關路徑的研究卻是非常有限。在本篇實驗中,我們將細部去討論心肌細胞的訊息傳遞路徑的改變。另外當餵食原兒茶酸(PCA)作為一治療方法,是否能對於心臟相關的訊息傳遞路徑有所改變。文中利用先天性高血壓老鼠(SHR),將這些高血壓老鼠分為高血壓組(SHR)與高血壓餵食PCA組(SHR-PCA)。每毫升含有0.01毫克的原兒茶酸,每公斤餵食0.2毫克的原兒茶酸混合於水,每週第一、三、五天餵食一次,一週餵食三次且共持續八週。對照組為Wistar Kyoto rats(WKY)。最後在餵食過程結束後,利用H&E staining和TUNEL assay和Western Blotting的實驗來觀察心肌細胞組織間和蛋白質間的變化。心肌細胞凋亡路徑包括death-dependent和mitochondria-depend路徑。在高血壓組別中(SHR),心肌細胞凋亡路徑的蛋白質表現量和對照組(WKY)相比較皆有顯著上升。而餵食原兒茶酸的組別(SHR-PCA),相較於沒有餵食PCA的高血壓組(SHR),凋亡相關路徑蛋白質表現量皆明顯下降。而在survival訊息傳遞路徑中蛋白質的表現量,高血壓組別(SHR)明顯的比對照組(WKY)低。而在餵食PCA 之後,蛋白質的表現量皆有明顯的上升。在高血壓的實驗中發現,餵食PCA可有效的抑制心肌細胞凋亡相關蛋白的表現量,並且促進survival的相關蛋白表現量,成功的保護了心肌細胞免於走向細胞凋亡的途徑。因此本篇的實驗發現原而茶酸可提供高血壓病人一個有效的預防心臟方面的併發症的發生。

關鍵字

心臟 高血壓 細胞死亡

並列摘要


Background. Activated cardiac apoptosis was found in hypertension but less information regarding the effects of protocatechuic acid on cardiac apoptosis in hypertension was available. The purpose of this study was to evaluate the anti-apoptotic and pro-survival effects of protocatechuic acid on hypertensive hearts. Methods. Eighteen spontaneously hypertensive rats, were divided into sedentary group(SHR) and underwent feeding PCA 0.01mg/ml,(0.2/kg BW) mixed in water,3 times per week(on the first ,third and fifth days of each week)for 8 weeks (SHR-PCA). Ten Wistar Kyoto rats as a sedentary normotensive group (WKY). After protocatechuic acid or sedentary status, the excised hearts were measured by H&E staining, TUNEL assay and Western Blotting. Results. TUNEL-positive apoptotic cells were increased in SHR groups and decreased in SHR-PCA groups. Protein levels of Fas ligand, Fas death receptor, Fas-associated death domain (FADD), Bid, t-Bid, Bax, cytochrome c, activated caspase-8, activated caspase 9 and activated caspase-3 were decreased in SHR-PCA group compared with SHR group. Protein levels of IGF1, IGF1R, p-PI3K, p-Akt, Bcl-xL, and Bcl-2 (cardiac pro-survival pathway) become more activated in SHR-PCA groups than SHR and WKY. Conclusions. Protocatechuic acid prevented hypertension-enhanced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced cardiac pro-survival pathway in rat models. Our findings demonstrate a new therapeutic effect of protocatechuic acid on hypertensive heart for preventing apoptosis and enhancing survival.

並列關鍵字

mitochondrial heart cell death hypertension Fas receptor caspase

參考文獻


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