心肌保護之類黃酮成分研究

Myocardial Protection of Flavonoids

黃麗文(Huang-Li Weng)

指導教授 ： 楊玲玲 ； 顏焜熒

臺北醫學大學/藥學院/生藥學研究所/碩士(2000年)

摘要

從1977年至1997間，心臟疾病一直高居國人十大死因第四位，近年來甚至高至第三位；造成心臟疾病的原因有很多，其中脂質過氧化作用(Lipid Peroxidation(LPO))是破壞心肌細胞主要原因之一。目前中草藥中，polyphenol類之成份已知具有很好的抗氧化效用，但是有關保護心臟方面的研究並不多，因此本實驗針對天然物中19種Flavonoids及1種Anthocyan之成份，分別以non-enzyme性之化學誘導劑tert-Butyl hydroperoxide (t-BuOOH) 、FeSO4以及enzyme性之誘導劑NADPH分別誘導心肌細胞粒線體(mitochondria)產生脂質過氧化作用，經由TBARS Methods，HPLC定量分析方法，利用LiChrospher 100RP-18e column 於532nm下偵測MDA (TBA)2，以Vit.E為對照組，評估藥物清除脂質過氧化之效果。利用此生物活性測定模式，結果顯示：Quercetin、Baicalein、Baicalin、Fisetin、Kaempferol、Myricetin、Morin、Quercetin pentaacetate、Quercitrin和Epicatechin於濃度0.167 mg/ml下皆具有明顯50%以上抑制作用，並呈現濃度依存性。其中以Quercetin的脂質過氧化抑制效果最好。因此，我們大量萃取分離槐花之主成分: Quercetin，探討其對Adriamycin(ADR)引起心臟毒性的作用，結果發現，經由CPK(Creatine Phosphokinase)及LPO定量試驗得知，Quercetin先投予後再投予ADR，鼷鼠血清之CPK值有明顯下降，心臟粒線體細胞之LPO值亦有明顯下降，因此證明Quercetin具有明顯的預防心肌受損作用，並呈現濃度依存性；而對於先投予ADR破壞心肌細胞後再投予Quercetin之治療效用評估，鼷鼠血清之CPK值以及心臟粒線體細胞之LPO值雖有下降，但只有Quercetin劑量30mg/kg呈現有意義之降低，因此證明Quercetin對於心肌受損後的治療效用不大。由研究結果得知，Quercetin之預防心肌受損作用大於治療，可提供臨床應用作為日後Adriamycin之輔助劑，降低其副作用，使其仍能廣泛應用於癌症病人的治療。

關鍵字

類黃酮 ； 心臟 ； 粒線體 ； 脂質過氧化 ； 高壓液相層析法

並列摘要

Polyunsaturated fatty acids are the major targets of oxidative attack and their unspecific oxidation, the lipid peroxidation, is a oxygen free radical-mediated pathway leading to a number of stable and toxic products. These biological membranes, especially mitochondria, may lead to rupture , so this study focus on the protection of mitochondria. Otherwise, much attention has been focused on the study of lipid peroxidation in relation to the pathogenesis of many degenerative diseases such as atherosclerosis , ischemic injury in myocardium, diabetes and in the process of aging , especially heart disease. So to find the efficacy of anti-lipid peroxidation to protect heart cell damage is very important. The lipid peroxidation measurement in rat heart mitochondria was induced by ascorbate-Fe2+ and NADPH, and assess anti-lipid peroxidative effects by thiobarbituric acid reactive substances (TBARS) method, then quantitative analysis of MDA(TBA)2 by high performance liquid chromatography. The nineteen kinds of natural occurring flavonoids and one kind anthocyan were investigated the lipid peroxidation inhibitory effects in this paper. In view of the results, seven of these natural occurring flavonoids were displayed significant potential inhibition from control group. There are quercetin , baicalein , fisetin , kaempferol , baicalin , epicatechin and myricetin were more potent than vitamin E. Especially, quercetin even showed 1000-fold higher than vitamin E. Furthermore, we extracted and isolated quercetin from Sophorae Flas , and tested its potency in ICR mice. We found that quercetin can protect heart tissue to against Adriamycin-induced cardiomyopathy in mice. These results suggest that Quercetin might be applicable as a protective agent against cardiotoxicity of Adriamycin.

並列關鍵字

Flavonoids ； Heart ； Mitochondria ； Lipid peroxidation ； Quercetin ； HPLC ； Adriamycin

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