International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149, Trieste, Italy.
Pediatr Res. 2020 Jan;87(1):17-25. doi: 10.1038/s41390-019-0570-x. Epub 2019 Sep 7.
The molecular and cellular events leading to bilirubin-induced neurotoxicity, the mechanisms regulating liver and intestine expression in neonates, and alternative pathways of bilirubin catabolism remain incompletely defined. To answer these questions, researchers have developed a number of model systems to closely recapitulate the main characteristics of the disease, ranging from tissue cultures to engineered mouse models. In the present review we describe in vitro, ex vivo, and in vivo models developed to study bilirubin metabolism and neurotoxicity, with a special focus on the use of engineered animal models. In addition, we discussed the most recent studies related to potential therapeutic approaches to treat neonatal hyperbilirubinemia, ranging from anti-inflammatory drugs, activation of nuclear receptor pathways, blockade of bilirubin catabolism, and stimulation of alternative bilirubin-disposal pathways.
导致胆红素诱导的神经毒性的分子和细胞事件、调节新生儿肝脏和肠道表达的机制以及胆红素分解的替代途径仍未完全定义。为了回答这些问题，研究人员开发了许多模型系统来密切重现疾病的主要特征，从组织培养到工程化的小鼠模型。在本综述中，我们描述了用于研究胆红素代谢和神经毒性的体外、离体和体内模型，特别关注工程动物模型的使用。此外，我们还讨论了与治疗新生儿高胆红素血症的潜在治疗方法相关的最新研究，这些方法包括抗炎药物、核受体途径的激活、胆红素分解的阻断以及替代胆红素处理途径的刺激。
