ISOPROSTANES: A MARKER OF OXIDATIVE INJURY IN NON-ALCOHOLIC FATTY LIVER DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 儿童肥胖症在美国是一种迅速流行的流行病。伴随着肥胖率的上升，非酒精性脂肪性肝病的发病率也在上升。据估计，NAFLD影响多达160万美国儿童。这些儿童中的一个亚组患有非酒精性脂肪性肝炎(NASH)，这是一种可能导致纤维化和肝硬化的侵袭性坏死性炎症性疾病。氧化损伤被认为是从良性脂肪变性发展为NASH的关键组成部分。由于缺乏可靠和非侵入性的氧化应激指标，对体内氧化损伤的彻底了解一直是困难的。近年来，对异前列腺素的测量显示出了希望。氧化应激引起的损伤可能是通过细胞因子传播的。 目的：1)建立血浆和尿异前列腺素作为儿童NAFLD/NASH氧化损伤标志物的应用价值。2)探讨儿童NAFLD/NASH氧化损伤与促炎和抗炎细胞因子的关系。 方法：研究对象包括3个年龄在10到18岁之间的患者：1)已知患有NAFLD/NASH的超重者，2)无肝病证据的超重者，3)无肝病的健康体重对照组。超重将被定义为身体质量指数(BMI)年龄段BMI大于95%。研究包括体检、人体测量学、人口学、ALT/AST、空腹胰岛素、血糖和血脂、血清瘦素和细胞因子。此外，还将分析尿液和血清中的异前列腺素。一些患者将接受腹部超声波检查。 分析：将进行适当的统计分析，以了解异前列腺素在儿童NAFLD/NASH研究中的效用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Childhood obesity is a burgeoning epidemic in the United States. Accompanying this rise in obesity, is a rise in non-alcoholic fatty liver disease. Estimates indicate that NAFLD affects up to 1.6 million American children. A subgroup of these children have non-alcoholic steatohepatitis (NASH), an aggressive necro-inflammatory disease that may lead to fibrosis and cirrhosis. Oxidative injury is thought to be a key component in the progression from benign steatosis to NASH. A thorough understanding of oxidant injury in vivo has previously been difficult because of a lack of reliable and noninvasive indexes of oxidant stress. In recent years, measurements of isoprostanes have shown promise. The injury initiated by oxidative stress may be propagated by cytokines. Aims: 1) To establish the utility of plasma and urinary isoprostanes as markers of oxidative injury pediatric NAFLD/NASH. 2) To explore the relationship of oxidative injury, as measured by plasma and urinary isoprostanes and pro-inflammatory and anti-inflammatory cytokines in pediatric NAFLD/NASH. Methods: Three patient populations, ages 10 to 18, will be studied: 1) overweight subjects known to have NAFLD/NASH, 2) overweight subjects without evidence of liver disease and 3) healthy weight controls without liver disease. Overweight will be defined as body mass index (BMI) BMI greater than 95%ile for age. Studies including a physical exam, anthropometrics, demographics, ALT/AST, fasting insulin, glucose and lipid profile, serum leptin and cytokines will be performed. Additionally, urinary and serum isoprostanes will be analyzed. Some patients will receive an abdominal ultrasound. Analysis: Appropriate statistical analysis will be performed to understand the utility of isoprostanes in the study of pediatric NAFLD/NASH.