2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647651摘要：早產兒因出生後臨床照護的需要治療而受到氧氣供給、機械換氣、發炎或感染等併發症容易產生活性氧化物質，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的集合，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。液相色譜法可用於檢測和定量大量的代謝物。近來利用代謝體學分析生物流體及組織，已經成功地運用在臨床研究中，相關的研究結果也可應用於探討疾病的致病機轉或辨識早期的生物標記。本研究為三年期計畫，將在台大醫院收集共240位非常低出生體重早產兒的各種生物檢體，分析各胎齡以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，諸如早產兒尿中的8-iso-prostaglandin Fα及8-hydroxydeoxyguanosine會被同時測量做為評估氧化壓力的相關生物指標，期能藉由氧化壓力的相關生物指標探討早產兒臨床疾病的相關性，以早期介入並減少早產兒長期之併發症。最後，我們另外收集各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: The prevalence of preterm birth remains around 10% of the general neonatal population in Taiwan despite the advance of perinatal care. In addition, 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.We will conduct a 3-year project to recruit totally 240 very low birth weight premature neonates and collect various biosamples including urine, blood and bronchoalveolar lavage fluid to analyze their metabolomic pattern at different time points. The association between metabolites changes and oxidative stress related disease in the premature infants will be explored and early biomarker predicting disease will be identified. Finally, we will collect 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. To investigate the oxidative stress in the neonates, the measurement of two oxidative products including 8-iso-prostaglandin Fα and 8-hydroxydeoxyguanosine (8-OHdG) had been proved the reliable tools for the identification of subjects with enhanced rates of lipid peroxidation and oxidative DNA damage respectively. The biomarkers of oxidative stress including 8-iso-prostaglandin F2α and 8- OHdG will be collected and analyzed in this study. The association between biomarkers and clinical diseases will also be investigated.The study goals are:1. To investigate the association between metabolomic profiling and gestational age.2. To identify the change of metabolomics profiling in the very low birth weight premature infants by postnatal age after birth3. To investigate the association between metabolomic pattern and prematurity oxidative stress related diseases (ROP/BPD)4. To investigate the association between oxidative stress biomarkers and oxidative stress related diseases5. To validate the association of identified metabolites and clinical diseases6. To investigate the relationship between identified metabolites, oxidative stress biomarkers and clinical diseases7. To identify significant early biomarkers associated with prematurity oxidative stress related diseases through integration of the metabolomic profiling from various biosamples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