2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647650摘要：早產兒因出生後臨床照護的需要，而受到氧氣供給、機械換氣、發炎或感染等併發症，易誘發活性氧化物質，進而產生自由基造成早產兒體內細胞的損傷，引發支氣管肺發育不良和早產兒視網膜病變。早產兒氧化壓力相關疾病的發生原因相當複雜，影響疾病進展的機轉仍存在許多未知的因素。代謝體為細胞、組織、體液或器官所含的小分子集合，涵蓋了各種生理代謝途徑之重要物質如胺基酸、核苷酸、脂肪酸等。代謝體分析可檢測和定量大量的代謝物，近年來，已應用於臨床研究，分析生物檢體，有助於探討疾病的致病機轉或辨識早期的生物標記。本研究在第一年上半年已完成核磁共振光譜學分析臍帶血中的代謝物，初步發現早產兒或出生體重低於妊娠週數的新生兒，在胺基酸和脂質的表現量具有獨特性；而 8-iso-prostaglandin Fα (8-iso-PGF2α)在早產兒的表現量較高；同時也確認血片可做為液相色譜法-質譜的分析。後續兩年半將完成台大醫院240位非常低出生體重早產兒的收案，分析各胎齡及出生後不同時間點其體內代謝體之分布情形，記錄早產兒罹病狀態，進而探討代謝體與早產兒氧化壓力相關疾病發生及致病之機轉。同時尋找重要的生物氧化標記，例如8-iso-PGF2α和8-hydroxydeoxyguanosine會被同時測量做為評估氧化壓力的相關生物指標，用於探討與早產兒臨床疾病的相關性，以期能早期預測或介入。我們亦規畫另外收集各40位被確認診斷為支氣管肺發育不良或早產兒視網膜病變的早產兒，進一步驗證特定代謝物與臨床疾病的相關性。<br> Abstract: Preterm newborns are subjected to several events leading to increased reactive oxygen species (ROS) production, as hyperoxia, mechanical ventilation, and inflammatory and infective complications. Free radicals and particularly oxygen-derived free radicals have been implicated as agents of cellular damage in many diseases associated with premature infants, including bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). The detail mechanisms involving the oxidative stress related disease remains unclear. Novel methodology to investigate the pathophysiology of oxidative stress related diseases in the premature infants is warranted.Metabolome consist of a large number of low molecular mass metabolites such as small peptides, amino acids, nucleic acids, fatty acids, hormones, etc. Among which, endogenous metabolites are commonly tied to specific biochemical pathway and reflect changes in pathways or process by distinguishable metabolite patterns. Liquid chromatography mass-spectrometry (LC-MS), which provides detection and quantification of a large set of metabolites, is proper technique for non-targeting “global” metabolomics. Recently, metabolomic analysis of biofluid or tissue has been successfully used in clinical studies for establishing accurate diagnosis, predicting prognosis, appropriate classification, or evaluating response to the therapy. Those results are important in the development of clarifying disease models, chemometrics, and ways to identify new biomarkers. To date, we have completed the analysis of 1H nuclear magnetic resonance (NMR) spectra using cord blood sample and found unique pattern of amino acid and lipid among preterm or small for gestational age neonates. We also identify significantly higher 8-iso-prostaglandin Fα (8-iso-PGF2α) in preterm babies. In addition, the validity of using dried blood spot for LC-MS based metabolomic analysis has been confirmed. In the coming two and half years, we will recruit totally 240 very low birth weight premature neonates and analyze their metabolomic pattern at different time points with various biological samples. The association between metabolomic profiling and oxidative stress related disease in the premature infants will be explored and early biomarker predicting disease will be identified. Meanwhile, two oxidative products including 8-iso-PGF2α and 8-hydroxydeoxyguanosine will be measured to represent the status of lipid peroxidation and oxidative DNA damage, respectively. The association between oxidative stress biomarkers and clinical diseases will also be investigated. Furthermore, we will recruit another 40/40 very low birth weight premature babies who have been diagnosed as ROP/BPD to validate the association of identified metabolites and clinical disease.早產代謝體學氧化壓力支氣管肺發育不良早產兒視網膜病變