FETAL MONKEY MODEL OF OBSTRUCTIVE RENAL DYSPLASIA

梗阻性肾发育不良胎猴模型

• 批准号: 6277900
• 负责人: Alice F Tarantal
• 金额: $ 5.99万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277900
• 关键词: Mammalia; Primates; congenital disorders; endocrine gland /system; growth /development; hormones; model design /development; mother /infant health care; ultrasonography; urinary tract

Significance Disorders of normal kidney development represent a major cause of renal failure and end stage renal disease (ESRD) in the pediatric population. Congenital anomalies such as prenatal urinary tract obstructions can have significant effects on renal function postnatally. Although congenital obstructive nephropathy is a major cause of chronic renal failure, little progress has been made towards understanding pathophysiologic mechanism(s) and developing methods for prevention and treatment. Objectives In order to further our understanding of the prenatal pathogenesis of renal dysplasia, develop markers to predict postnatal compromise and disease, and design interventive strategies for improving the outcome of obstructive nephropathy and renal dysplasia, a fetal monkey model that closely parallels human development and disease is being studied. Results An ultrasound-guided technique has been developed for inducing unilateral ureteral obstruction in the fetal monkey during the early second trimester, when active nephrogenesis is in progress. In utero renal anatomical and hemodynamic changes, and effects on fetal urine and amniotic fluid volume and biochemistry are monitored post-obstruction. Both non-obstructed and obstructed fetal monkey kidneys are studied to evaluate the histopathologic progression of obstructive nephropathy, and to determine the pattern of expression of insulin-like growth factor (IGF) genes and apoptotic markers. Initial studies have shown that the expression of IGF and IGF binding protein (IGFBP) mRNAs in the fetal monkey kidney are identical to that in human under normal developmental conditions. Since preliminary evidence suggests that the histopathologic progression of multicystic renal dysplasia includes an alteration in the pattern of expression of IGF-II, IGFBP-2, and IGFBP-3, this implies that IGF and IGFBP gene expression is intimately associated with the development and progression of multicystic dysplastic changes over time. Future Directions To characterize the developmental changes associated with obstruction, and investigate novel in utero approaches for reversing and/or preventing the abnormalities associated with disease. KEYWORDS fetus, kidney, IGF-II, IGFBP-3, apoptosis, obstructive uropathy

正常肾脏发育的显着性障碍代表 肾衰竭和终阶段肾脏疾病（ESRD）的主要原因 小儿种群。 先天性异常，例如产前尿 道障碍可能会对肾功能产生重大影响 产后。 尽管先天性阻塞性肾病是主要的 慢性肾衰竭的原因，对 了解病理生理机制和开发方法 预防和治疗。 目标以进一步 了解肾脏发育不良的产前发病机理，发展 预测产后妥协和疾病的标记，并设计 改善阻塞性结果的干预策略 肾病和肾脏发育不良，一种紧密的胎儿猴子模型 正在研究人类发展和疾病。 结果 超声引导的技术已开发用于诱导单方面的技术 第二次早期，胎儿猴子的输尿管阻塞 妊娠中期，当活动肾病正在进行时。 在子宫肾 解剖学和血液动力学变化，以及对胎儿尿液的影响 羊水体积和生物化学受到监测后的攻击后。 研究了非膜结构和阻塞的胎儿猴肾脏 评估阻塞性肾病的组织病理学进展， 并确定胰岛素样生长的表达方式 因子（IGF）基因和凋亡标记。 最初的研究表明 IGF和IGF结合蛋白（IGFBP）mRNA的表达 胎儿猴肾与正常人的人相同 发展条件。 由于初步证据表明 多细胞性肾脏发育不良的组织病理学进展 包括对IGF-II表达模式的改变， IGFBP-2和IGFBP-3，这意味着IGF和IGFBP基因表达 与 多细节的发育不良随着时间的变化。 未来的指示 表征与阻塞相关的发展变化， 并在子宫方法中调查小说的逆转和/或 防止与疾病相关的异常。 关键词胎儿， 肾脏，IGF-II，IGFBP-3，凋亡，阻塞性尿道病