人巨细胞病毒(human cytomegalovirus, HCMV)是人群中广泛感染的机会致病病毒，可导致胎儿及艾滋病患者中枢神经系统损害，研究其损伤机制具有重要意义。已知HCMV感染对细胞的直接损伤及其诱导的炎症反应可破坏血脑屏障，引起中枢神经系统损伤。前期研究显示HCMV可损伤先天性感染小鼠血脑屏障，并激活血管内皮细胞中NLRP3介导的炎性通路。为了证实NLRP3介导的炎性反应参与HCMV诱导的血脑屏障损伤，我们拟选择血脑屏障主要功能细胞为研究对象，采用RNA干扰技术研究NLRP3炎症小体在HCMV感染细胞中的作用，比较NLRP3炎症小体在不同细胞中效应；同时构建血脑屏障体外模型，检测HCMV激活NLRP3对血脑屏障通透性的影响；利用NLRP3基因敲除小鼠，在HCMV先天性感染模型上明确NLRP3炎症小体对血脑屏障的影响，为揭示HCMV宫内感染引起新生儿中枢神经发育畸形提供理论依据。

Human cytomegalovirus (HCMV) is the leading viral cause of congenital birth defects and is responsible for morbidity and mortality in immunosuppressed individuals such as neonates, sufferers of HIV /AIDS and transplantation recipients. Central nervous system abnormalities are associated with HCMV –induced immune injury and tissue damage. However, the mechanism of HCMV damaging the central nervous system remains unclear. The blood-brain barrier (BBB) is the body's main line against pathogens that attack the central nervous system. Previous studies have confirmed that HCMV could infect human blood-brain barrier function cells, and induce the release of inflammatory cytokines, including IL-1β and IL-18. And the NLRP3 was activated by HCMV in vascular endothelial cells. And blood-brain barrier permeability increased in HCMV-infected newborn mice.Thus, we speculate that NLRP3-mediated inflammatory responses are involved in HCMV-induced BBB injury. To confirm it, we will knockdown NLRP3 in blood-brain barrier function cells and mice to study the central role of neuroinflammation in neurological disorders induced by HCMV infection. It will provide a mechanism to better understand neonatal deformity of central nervous system caused by HCMV intrauterine infection.