围产医学发展，早产、围产期感染等高危儿增多，发育中脑的损伤备受关注；胆红素脑病是新生儿高胆红素血症最严重的并发症，病死率较高，幸存者常遗留神经系统后遗症，因发病机制不明，目前尚无安全有效的防治措施。研究表明，炎症反应在多种神经系统疾病发生中起重要作用，焦亡是caspase-1依赖的伴随高度炎症反应的细胞程序性死亡，逐渐受到关注。前期研究发现：①胆红素脑病发生过程中存在NF-κB激活及炎症反应；②胆红素诱导原代神经元及星形胶质细胞caspase-1活化、细胞焦亡，抑制NF-кB活性可抑制caspase-1活化。本项目拟在不同成熟度、不同类型的神经细胞及胆红素脑病动物模型上探究：①焦亡参与胆红素脑病的发生；②NF-кB是胆红素诱导神经细胞焦亡的关键因子。以期从调控焦亡入手，抑制胆红素神经毒性，为防治胆红素脑病提供新策略，为防治早产、围产期感染、氧浓度异常等引起的发育中脑的损伤提供新思路。

Recently, more and more high-risk infants suffering from prematurity, perinatal infection or hypoxia survive because of the great advancements in perinatal medicine. Consequently, the damage of developing brain draws more and more public attention. Bilirubin encephalopathy, as the most severe complication of neonatal hyperbilirubinemia, with a high mortality rate, may lead to neurological impairments, such as choreoathetoid cerebral palsy, sensorineural deafness, epilepsy and so on. However, there is still no cost-effective approach to prevent bilirubin encephalopathy because the pathogenesis remains largely unknown. Nowadays, the abundant evidences demonstrated that inflammation plays a critical role in many diseases of nervous system. Pyroptosis, as a highly inflammatory form of programmed cell death, involving the activation of enzyme caspase-1, has become a widespread issue of concern. Our previous studies indicated that Nuclear factor kappa B (NF-κB) activation and inflammatory response involved in the pathogenesis of bilirubin encephalopathy, moreover, caspase-1 activation and pyroptosis could be induced by unconjugated bilirubin in primary cultured neurons and astrocytes, whereas the caspase-1 activation was suppressed by inhibition of NF-κB. This study was intended to get a deeper insight into the involvement of pyroptosis in the pathogenesis of bilirubin neurotoxicity and to explore whether NF-κB is the critical factor of UCB-induced pyroptosis in the different types of nerve cells with different mature degrees and in the newborn rat kernicterus model. Thus, it might provide a novel and promising strategy for treating bilirubin encephalopathy, by suppressing the bilirubin neurotoxicity which could be achieved by regulating the pyroptosis, making it possible to prevent the developing brain damage related to the prematurity, perinatal infection and abnormal oxygen concentration.