KLF6通过自噬调控IL-23分泌在急性肝衰竭中的作用及机制研究

急性肝衰竭（ALF）是临床常见的威胁人类生命的肝病症候群，其致死率极高，发病机制较为复杂，主要为免疫介导的肝损伤，然而，其免疫学机制仍不甚清楚。前期研究证实：慢加急肝衰竭患者中，interleukin（IL）-23表达水平显著升高，其水平与疾病严重程度密切相关；在急性肝衰竭的小鼠模型中，IL-23中和抗体可显著减轻急性肝衰竭的严重程度；且急性肝衰竭小鼠模型中，krüppel样因子6（KLF6）的表达上调，自噬水平降低，过表达KLF6后，自噬水平降低，IL-23的分泌升高。故推测：KLF6通过自噬调控IL-23的表达影响ALF的进展。因此，本课题拟以此为基础，以急性肝衰竭小鼠模型为研究对象，综合运用细胞生物学和分子生物学等多项技术手段，从细胞和动物水平阐明KLF6通过自噬调控IL-23的分泌对ALF预后的影响，从而为ALF患者寻找新的诊疗思路或干预靶点。

Acute liver failure (ALF) is a common clinical liver disease that threatens human health. However, its immunological mechanism is still unclear. Our previous study proved that increased interleukin（IL）-23 secretion was closely related to disease progression in acute on chronic liver failure patients. Animal models showed that IL-23 neutralizing antibody could significantly reduce the severity of acute liver failure. Moreover, the expression of krüppel like factor 6 (KLF6) was upregulated and the level of autophagy decreased in ALF animal models. After overexpression of KLF6, the level of autophagy reduced and the secretion of IL-23 increased. Therefore, we speculate whether KLF6 could affect the prognosis of ALF by regulating the expression of IL-23 through autophagy. Based on these results, we plan to explore the expression of KLF6, autophagy and IL-23 at cell and animal levels by applying techniques of cell biology and molecular biology as to provide new diagnostic, therapeutic ideas or immunotherapy targets for ALF patients.