Metabolomic Analysis of Lung in Intrauterine Growth Restricted Rats

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Title:	Metabolomic Analysis of Lung in Intrauterine Growth Restricted Rats
Authors:	YULIANA, MERRYL ESTHER
Contributors:	國際醫學研究博士學位學程陳中明
Keywords:	metabolomic?analysis;omics;intrauterine?growth?restriction;lung?development metabolomic?analysis;omics;intrauterine?growth?restriction;lung?development
Date:	2023-12-20
Issue Date:	2024-11-06 13:34:23 (UTC+8)
Abstract:	IUGR, or intrauterine growth restriction, frequently arises as a consequence of uteroplacental insufficiency (UPI). The restriction of oxygen and nutrient transfer has been associated with impaired fetal lung development. IUGR and its associated complications pertaining to pulmonary development continue to be a significant contributor to adverse outcomes in both fetal and neonatal populations. Animal models of IUGR have demonstrated modifications in lung development. However, the precise impact of IUGR on metabolic alterations in the lungs remains uncertain. Nevertheless, the current prenatal screening methods for IUGR are limited due to the absence of comprehensive biomarkers, particularly those associated with pulmonary development. In response to this issue, novel methodologies such as omic biomarkers, including metabolomics, which encompass the analysis of a collection of molecular information, have emerged within the past few decades. The main aim of this study is to investigate the alterations in metabolic processes within lung tissues of IUGR rats through the utilization of metabolomic analysis. The lungs of the IUGR rats were procured for histological examination, Western blot analysis, and metabolomic analysis. Blood samples were obtained from the cardiac region in order to assess the concentrations of leptin. Liquid chromatography-mass spectrometry (LC-MS) was employed for the purpose of conducting metabolomic analysis. On postnatal days 0 and 7, it was observed that newborn rats with IUGR exhibited a statistically significant decrease in both average birth weight and body weight compared to the control group of newborn rats. In contrast to the control group of neonatal rats, the IUGR subjects exhibited a statistically significant decrease in the mean radial alveolar count (RAC), alveolar wall volume fraction, and proliferating cell nuclear antigen (PCNA). Conversely, the alveolar space volume fraction was greater in IUGR rat offspring. The neonatal rats with IUGR exhibited decreased levels of vascular endothelial growth factor (VEGF) expression, von Willebrand factor (vWF) immunoreactivity, vascular density, platelet-derived growth factor-A (PDGF-A), PDGF-B, leptin concentration in serum, lung leptin, and leptin receptor levels, compared to the control group. Metabolomic analysis revealed the presence of 14 statistically significant features within the pathways. Regarding significant differential metabolites, a total of 10 metabolites exhibited substantial variations between control and IUGR rats, with a statistical significance level of p < 0.05. The aforementioned findings demonstrate alterations in metabolic processes and underscore the significance of amino acid metabolism. The group studying IUGR discovered noteworthy associations among serum leptin levels, radial alveolar count, von Willebrand Factor levels, and metabolites. IUGR, or intrauterine growth restriction, frequently arises as a consequence of uteroplacental insufficiency (UPI). The restriction of oxygen and nutrient transfer has been associated with impaired fetal lung development. IUGR and its associated complications pertaining to pulmonary development continue to be a significant contributor to adverse outcomes in both fetal and neonatal populations. Animal models of IUGR have demonstrated modifications in lung development. However, the precise impact of IUGR on metabolic alterations in the lungs remains uncertain. Nevertheless, the current prenatal screening methods for IUGR are limited due to the absence of comprehensive biomarkers, particularly those associated with pulmonary development. In response to this issue, novel methodologies such as omic biomarkers, including metabolomics, which encompass the analysis of a collection of molecular information, have emerged within the past few decades. The main aim of this study is to investigate the alterations in metabolic processes within lung tissues of IUGR rats through the utilization of metabolomic analysis. The lungs of the IUGR rats were procured for histological examination, Western blot analysis, and metabolomic analysis. Blood samples were obtained from the cardiac region in order to assess the concentrations of leptin. Liquid chromatography-mass spectrometry (LC-MS) was employed for the purpose of conducting metabolomic analysis. On postnatal days 0 and 7, it was observed that newborn rats with IUGR exhibited a statistically significant decrease in both average birth weight and body weight compared to the control group of newborn rats. In contrast to the control group of neonatal rats, the IUGR subjects exhibited a statistically significant decrease in the mean radial alveolar count (RAC), alveolar wall volume fraction, and proliferating cell nuclear antigen (PCNA). Conversely, the alveolar space volume fraction was greater in IUGR rat offspring. The neonatal rats with IUGR exhibited decreased levels of vascular endothelial growth factor (VEGF) expression, von Willebrand factor (vWF) immunoreactivity, vascular density, platelet-derived growth factor-A (PDGF-A), PDGF-B, leptin concentration in serum, lung leptin, and leptin receptor levels, compared to the control group. Metabolomic analysis revealed the presence of 14 statistically significant features within the pathways. Regarding significant differential metabolites, a total of 10 metabolites exhibited substantial variations between control and IUGR rats, with a statistical significance level of p < 0.05. The aforementioned findings demonstrate alterations in metabolic processes and underscore the significance of amino acid metabolism. The group studying IUGR discovered noteworthy associations among serum leptin levels, radial alveolar count, von Willebrand Factor levels, and metabolites.
Description:	博士指導教授：陳中明口試委員：陳中明口試委員：曹伯年口試委員：鄭玫枝口試委員：莊校奇口試委員：黃亮迪
Note:	論文公開日期：2024-01-11
Data Type:	thesis
Appears in Collections:	[International Master/Ph.D. Program in Medicine] Dissertations/Theses

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