肝衰竭是多种原因引起的以凝血机制障碍、黄疸、肝性脑病、腹水为表现的临床症候群，死亡率高。过度炎症引起的免疫性损伤是该病主要发病机制，目前对过度炎症发生的机制尚不完全清楚。CYLD是去泛素化酶家族一员，对NF-kappaB相关的炎症通路起负调控作用。课题组前期工作发现在肝衰竭患者的血清中miRNA-222表达升高且与凝血酶原时间延长显著相关，在患者PBMC中发现CYLD表达下降，且CYLD极有可能为miRNA-222的靶位基因。本研究拟通过细胞功能实验和急性肝衰竭动物模型验证分析miRNA-222通过作用靶位基因CYLD调控NF-kappaB通路激活和相关细胞因子分泌；并建立前瞻性队列分析患者血清miRNA-222的表达对病情进展和预后的影响。这些研究将阐明肝衰竭中miRNA-222可能通过调节靶位基因CYLD影响NF-kappaB通路，造成过度炎症因子分泌，为治疗肝衰竭提供新的理论和策略。

Liver failure is a severe inability of the liver to perform its normal synthetic and metabolic function, as clinically characterized by jaundice, ascites, encephalopathy and coagulopathy, which may lead to multiple organ failures and death. The excessive inflammatory response plays a pivotal role in the pathogenesis of liver failure, but the mechanisms involved are still remain not fully understood. The cylindromatosis gene CYLD is a cornerstone of the inflammatory response and could control over NF-kappaB mediated inflammation. Preliminary work of our group found that the serum miRNA-222 levels were significantly higher in liver failure patients and have positive correlation of prothrombin time. The PBMC CYLD levels reduced in liver failure patients, and CYLD may be the direct target of miRNA-222. Our study is supposed to verify miR-222 acts through CYLD to activate the NF-kappaB signaling pathway in cell lines and in vivo model; build a prospective cohort to analyze serum miRNA-222 levels with the prognosis of liver failure patients. This study help identify the novel mechanism of miRNA-222 acts through CYLD to activate the NF-kappaB pathway and to develop new insights on the liver failure therapy.