非酒精性脂肪性肝病（NAFLD）的流行率逐年升高，其自然史包括非酒精性脂肪肝（NAFL）、非酒精性脂肪性肝炎（NASH）、并可能经过肝脏纤维化最终进展成肝硬化和肝细胞癌（HCC），严重危害人类健康。炎症是NASH有别于肝脏脂肪变的主要标志，而NASH的炎症与脂肪变有关。研究表明STING-TBK1信号通路参与了感染和免疫相关疾病的炎症反应，同时STING-TBK1信号通路参与了脂肪代谢的调节。我们的前期研究发现STING-TBK1信号通路蛋白分子参与了小鼠NAFLD肝脏炎症和长链脂肪酸的合成。但是关于该通路在NAFLD肝脏炎症和脂肪变的具体分子机制尚不清楚。本研究拟通过NAFLD动物模型和NAFLD人群肝组织来研究和验证STING-TBK1信号通路的关键机制与NAFLD肝脏脂肪变及炎症发生、发展和消退的相关性, 可能会提出NAFLD发生发展的新机制。

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing gradually, and its natural history includes non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), liver fibrosis and hepatocellular carcinoma (HCC). So human health will be endangered seriously in the process from NASH to HCC. At present, the pathogenesis of NAFLD is not clear completely. Inflammation is the major feature of NASH that is different from steatosis, and inflammation of NASH is associated with steatosis. Studies have shown that STING-TBK1 signaling pathway is involved in the inflammatory response of infected and immune-related diseases, and STING-TBK1 signaling pathway is related to the regulation of fat metabolism. Our previous study found that STING-TBK1 signaling pathway is involved in liver inflammation and long-chain fatty acid synthesis in mouse NAFLD. But the important role of STING-TBK1 signaling pathway in the pathogenesis of NAFLD inflammation and lipid metabolism is not clear completely. In this study, we will illustrate and verify the relationship between the key mechanisms of STING-TBK1 signaling pathway and the occurrence, development and regression of hepatic steatosis and inflammation in NAFLD mouse model and NAFLD population, it may propose a new mechanism for the occurrence and development of NAFLD.