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標題: 天然類黃酮化合物對高度糖化終產物引發生物體氧化傷害、促發炎反應與細胞凋亡之評估
Effects of Flavonoids on Ages-Induced Biological Oxidative Damage, Pro-Inflammatory Response and Cell Apoptosis
作者: 顏國欽
關鍵字: 基礎研究;Flavonoids, advanced glycation end products (AGEs),oxidative damage, pyrraline, pro-inflammatory, apoptosis.;食品科技;高度糖化終產物;氧化傷害;促發炎反應;細胞凋亡;類黃酮化合物
糖尿病是相當錯綜複雜的全身代謝疾病,最終是影響全身大小血管。關於糖尿病併發症之發展機制,許多證據皆指向具糖毒性 (glycotoxins) 之高度糖化終產物 (advanced glycation end products; AGEs)。高度糖化終產物之毒性效應會促進人類重要細胞如血管內皮細胞等細胞氧化傷害、程序性凋亡以及細胞功能缺損等,造成糖尿病心血管等併發症。其主要機制乃因氧化壓力上升導致促發炎反應,更進一步引發細胞DNA 傷害。理論上補充抗氧化劑來逆轉糖尿病人體內居高不下之氧化壓力與抑制高度糖化終產物所造成之毒性效應,應為防預糖尿病併發症之可能策略。文獻對於生物體糖化作用所造成的負面作用,其解決辦法仍停留在阻斷AGEs 生合成。生物體內已累積的 AGEs 所造成的氧化傷害,仍未見相關文獻資料以天然抗氧化物角度進行探討。因此本研究計畫擬針對AGEs,以類黃酮化合物為研究材料。以體外及體內試驗模擬高度糖化終產物累積於生物體所造成的生理效應來進行探討。研究計畫擬分三年進行,第一年度以商業化之高度糖化終產物S100B protein 誘導人類單核球細胞為模式,模擬糖尿病氧化壓力上升而引發促發炎反應之生理狀態;介入類黃酮化合物,評估其抑製作用及調控機制。同時自行合成人體內普遍存在之典型高度糖化終產物 pyrraline,並進行鑑定。第一年建立類黃酮化合物抑制糖尿病因氧化壓力而促進促發炎反應之體外試驗平台後。第二年以體外及體內試驗平台評估類黃酮化合物及其天然富含物對典型高度糖化終產物pyrraline 引發生物體氧化傷害之效應。觀察類黃酮化合物對細胞 DNA 氧化傷害及糖尿病動物體內組織傷害;抗氧化、抗凋亡等基因表現;抗氧化酵素;AGEs 解毒酵素活性與糖尿病鼠體內pyrraline 含量之影響。第二年度實驗結果將可以同時瞭解天然抗氧化物於體內及體外試驗,對典型高度糖化終產物導致生物體氧化傷害之保護效應。第三年度則以pyrraline 對細胞DNA 氧化傷害為平台,進一步探討因氧化傷害所引起之程序性凋亡效應及其分子機制。為期三年之計畫將可以完整瞭解,類黃酮化合物對於高度糖化終產物累積,引發生物體氧化傷害之保護效應。研究成果極具健康食品之參考價值。

Diabete mellitus is a complex disease of metabolism which will influencevascular tissue. Many evidences have indicated that advanced glycationend products (AGEs) is one of the most important mechanism of diabeticcomplication. AGEs is charactered of glycotoxin which could induceoxidative damage, cell programmed apoptosis and cell dysfunctionresulting in diabetes complication of atherosclerosis. Involvement of themechanism is because of AGEs induces oxidative stress leading topro-inflammatory response and then resulting in cellular DNA oxidativedamage. In theory, the strategy of prevention of diabetic complication isusing the antioxidants to inhibit oxidative stress and AGEs toxicity indiabetic patients. In literatures, the prevention of biological glycationdamage is still remained to block the formation of AGEs. However, thedata concerning the effects of naturally occurring antioxidants on AGEsaccumulated leading to oxidative damage in diabetes is limited. Thepurpose of this three year』s project is to investigate this problem asdescribed above. In the first year』s plan, the naturally occurringantioxidants, flavonoids, will be used to monitor the protective effects ofnaturally occurring antioxidants against commercial-AGEs (S100Bprotein) mediated oxidative damage and pro-inflammatory responses inhuman monocytes. This approach expects to realize whether flavonoidsreduce oxidative stress and pro-inflammatory reponse in the diabeticmodel in vitro. In addition, the typical AGEs commonly detected indiabetic patients, pyrraline, will also be prepared and purified for theexperiment of the second year. In the second year』s plan, both the cell andanimal model systems will be used to evaluate the inhibitory effects offlavonoids on AGEs-induced oxidative damage in vitro and vivo. Thisapproach is to investigate the effects of flavonoids on AGEs-inducedcellular DNA oxidative damage, biological tissue damage, antioxidantand anti-apoptosis gene expression, and antioxidant enzymes, glyoxalaseI levels and the AGEs contents in diabetic rats. In the third year』s plan,the molecular mechanism of flavonoids on AGEs-induced cell apoptosiswill be investigated. The overall project expects to realize whetherflavonoids could reduce oxidative damage observed in the model ofdiabetic AGEs accumulation. The results of this three year』s project willbe useful for human health.
其他識別: NSC96-2628-B005-004-MY3
Appears in Collections:食品暨應用生物科技學系

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