2021-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/692257敗血症的高死亡率常起因於延遲診斷和隨之而來的器官損害。目前用於疾病診斷的常規血清生物標記皆依賴抗體來進行檢驗，當因應疾病治療需要進行連續生物標記檢驗時，將增加臨床醫療的成本。因此，需要一種無抗體試劑的方法來協助臨床早期篩選疾病，並且於病患治療期間得以連續監測急性細胞因子風暴。之前通過使用大鼠腸系膜上動脈阻塞模型，我們已在體內和體外試驗中發現，器官缺血將造成血清中的自體黃色螢光明顯增加。根據我們最新的研究發現：一氧化氮合酶、乳酸脫氫酶與腎素，這三種酵素和敗血症病患的血清自體螢光增加相關。此外，根據我們對敗血症患者血清樣本的初步研究，自體螢光數據結果與我們的文獻探討結果相符；意即我們發現自體螢光強度與敗血症的嚴重程度有關。基於我們對血清螢光體特徵的最新發現，在本提案中，我們不僅將繼續在敗血症的血液樣本中測定更多的自體螢光光譜特徵，也將整合來自螢光光譜儀與螢光基礎之高效液相層析質譜儀兩者的分析資料，進一步探索自體螢光來源。自體螢光來源分析有助我們了解前述於敗血病患治療過程中所觀察到的自體螢光變化，進而驗證自體螢光與病患治療成效之關聯性，以求將自體螢光檢測發展為用於敗血症預後之創新工具。 High mortality resulting from late diagnosis and consequent organ damages is common in sepsis. Currently, routine tested serum markers rely on antibodies to diagnose diseases so that it can be costly when serial testing is needed for disease management. Therefore, an agent-free approach to early screen and continuously monitor the acute cytokine storms is demanded. Previously, by using superior mesenteric artery occlusion model of rat, we found an obvious increase of yellow fluorescence in serum right after mesenteric ischemia in vitro and in vivo. Recently, we identified three hallmark enzymes: nitric oxide synthase (NOS), lactate dehydrogenase (LDH), and renalase, responsible for the increased fluorescence in sepsis. Moreover, according to our preliminary study data in sepsis patient samples, the results matched our literature review findings. Namely we found that the auto-fluorescence intensity was associated with the severity of sepsis. Based on our updated findings in serum fluorescent features, in this proposal, we not only continue to discover more spectroscopic features in blood samples of patients with sepsis, but also aim to explore the source of auto-fluorescence by synergized analytical results gained from fluorescence spectroscopy and fluorescence-based HPLC (high performance liquid chromatography) -tandem mass spectroscopy. The source analysis will help us to learn the auto-fluorescence dynamics we observed in sepsis patients during treatment. Subsequently, we will be able to validate the correlation between auto-fluorescence and patient outcome and in turn develop it to be a novel tool for sepsis prognosis.血液螢光體自體螢光敗血症FluorochromicsAuto-fluorescenceSepsis