TAT-NBD及ERK通路防治胆红素神经毒性的研究

项目名称： TAT-NBD及ERK通路防治胆红素神经毒性的研究

项目编号： No.81200459

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 华子瑜

作者单位： 重庆医科大学

项目金额： 21万元

中文摘要： 围产医学发展，窒息、早产等病理性黄疸高危新生儿存活率明显增加；其严重并发症-胆红素脑病的发生近年有回升趋势，此病病死率较高，幸存者常遗留学习、记忆障碍等神经系统后遗症。海马与学习、记忆有密切联系。本研究取胎鼠海马组织进行神经元原代培养研究，明确胆红素诱导的NF-κB活化是否具有时间依赖性；ERK是否通过抑制NF-кB的早期活化、增强其晚期活化，抑制胆红素诱导的海马神经元凋亡。同时，经小脑延髓池注射胆红素建立新生大鼠胆红素脑病模型，探讨适时、适量的腹腔内注射TAT-NBD，是否可抑制胆红素诱导的海马组织NF-κB 早期活化，减轻海马区细胞凋亡及炎症损伤，改善胆红素脑病大鼠的学习记忆能力。从调控凋亡的上游细胞信号传导系统入手，寻找抑制胆红素的神经毒性、防治胆红素脑病新方法，进而为防治早产、围产期异常氧浓度、感染等引起的新生儿脑损伤提供新策略。

中文关键词： TAT-NBD；NF-κB；胆红素；神经毒性；

英文摘要： As time on, more and more exciting progresses are being made in field of perinatal medicine. Therefore, large number of small preterms and asphyxia newborn babies are survived, and all of them are in high risk of pathological hyperbilirubinemia. So the incidence of bilirubin encephalopathy, the severe complication of neonatal jaundice, increases in recent years. Bilirubin encephalopathy shows high mortality and morbodity. Most patient may die or partially survive with sequelae of nervous system, such as academic handcap and memory difficulty. Hippocampal neuron is proved closely-related to learning and memory. The primary culture is performed with hippocampal neurons of fetal mouse. We investigate whether bilirubin-induced activation of neuronal NF-κB is time-dependent whereas ERK pathway suppresses bilirubin-induced neuron apoptosis by influencing the dual role of neuronal NF-κB. Meanwhile, we employe mouse model of bilirubin encephalopathy to investigate when intraperitoneal injection of optimal dose of TAT-NBD does depress bilirubin-induced neuron apoptosis by regulating neuronal NF-κB pathway. Based on the study about cellular signal conduction system relating to apoptosis regulation, we try to figure out a new strategy to protect neuron against bilirubin toxicity, making it possible to effectively prevent n

英文关键词： TAT-NBD；NF-κB；bilirubin；neurotoxicity；