利用可疏水性轉換之螢光標定蛋白水解酵素基質探針以非侵犯性造影活體腸道發炎疾病

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題名:	利用可疏水性轉換之螢光標定蛋白水解酵素基質探針以非侵犯性造影活體腸道發炎疾病 Noninvasive imaging of Inflammatory bowel by hydrophobic conversion of a fluorescent protease substrate
作者:	楊登超 Yang, Deng-Chao
貢獻者:	生藥學研究所
關鍵詞:	發炎性腸道疾病;基質金屬蛋白酶-2 Inflammatory bowel disease;Matrix metalloproteinase-2
日期:	2015-11-14
上傳時間:	2020-12-31 11:37:43 (UTC+8)
摘要:	腸道發炎疾病(Inflammatory bowel disease, IBD)是國人近年來的通病，嚴重者可能造成腸穿孔，一旦發現此類疾病，不易治癒會反覆發作。過去開發治療IBD的藥物常利用IBD小鼠動物模型去評估治療藥物的療效但往往需要大量的實驗老鼠、花費大量的金錢和消耗大量的時間來得到結果，對於藥物的開發極於曠日費時。為了解決上述問題，本實驗我們以IBD發生時基質金屬蛋白酶-2 (Matrix metalloproteinase-2 , MMP-2)表現量會增加的現象，利用已經成功開發出的PEG- MMP-2 peptide-TMR進行各項活體內外的測試，從體外試驗可觀察出此造影劑可經由IBD發生時常見的白血球浸潤及刺激纖維母細胞的情形會表現大量活化態MMP-2而後對此造影劑進行水解並累積於發炎區域，在活體內試驗也可得到具有腸道發炎的老鼠組別有較強的螢光累積情形，並對腸道發炎組織和參與腸道發炎相關細胞進行活化態MMP-2 蛋白質測定，結果顯示腸道發炎情形會提高活化態MMP-2 蛋白質表現量，藉此可以利用本實驗結果應用於IBD藥物的開發，此造影劑可連續且即時偵測老鼠腸道組織的恢復情或發炎的情況，經由螢光累積特性快速且確實的推論出治療藥物的功效，大幅減少實驗鼠與金錢的花費，加速藥物的開發。 Inflammatory bowel disease (Inflammatory bowel disease, IBD) is a common problem for people in recent years and severe cases may cause intestinal perforation. Once people get IBD, it is difficult to cure and have recurrent trouble easily. In order to develop therapeutic drugs of IBD, IBD animal model is often used to evaluate the efficacy of therapeutic drugs in the past, but it often requires a lot of experimental mice, spend a lot of money and consume a lot of time to get experimental results that will be time consuming. In order to solve these problems, we have shown that the expression of activated MMP-2 in IBD animal model was increased. The PEG- MMP-2 peptide-TMR has been successfully developed in vivo and in vitro experiments. When IBD occurs, Leukocyte infiltrates and stimulates fibroblast cells to produce large numbers of activated MMP-2 form in vitro. Then hydrolysis of PEG- MMP-2 peptide-TMR by MMP2 and accumulated in the inflamed area. IBD animal model group has a strong fluorescence accumulation in vivo. Activated MMP-2 protein is measured for inflammatory bowel tissue and intestinal inflammation associated cells. The results showed that the intestinal inflammation situation will increase the amount of activated MMP-2 protein expression. We can take advantage of the experimental results applied to the development of IBD drugs. This PEG- MMP-2 peptide-TMR can continuously and immediately detect the recovery situation or Inflammatory conditions of intestinal tissue of mice. Fast and reliably infer the efficacy of the therapeutic agent by accumulations of PEG- MMP-2 peptide-TMR. Finally, accelerate the development of drugs by reducing the cost of money and only a few mice.
描述:	碩士指導教授:莊國祥委員:李美賢委員:鄭添祿
資料類型:	thesis
顯示於類別:	[生藥學研究所] 博碩士論文

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