长链非编码RNA（lncRNA）在肝纤维化中的调控作用尚不清楚。我们前期研究显示人肝星状细胞（HSC）和肝硬化患者中lncRNA4166及其顺式基因心脏神经嵴衍生表达转录子2（HAND2）增高、靶基因miRNA92a降低；它们协同参与了HSC活化而具有促肝纤维化的作用。本课题拟从细胞水平用质粒过表达和siRNA干扰lncRNA4166-miRNA92a-HAND2轴基因，探索其对HSC活化、凋亡等多种生物学功能和下游肝纤维化靶信号通路的影响。并构建Floxed基因法肝脏特异性HAND2敲除鼠和CCl4、DEN肝纤维化鼠模型，从体内角度阐述抑制lncRNA4166、HAND2或去阻谒miRNA92a逆转肝纤维化的作用。最后观察在不同病因慢性肝病中这些基因的表达及与预后的关联。研究结果将有助于从lncRNA4166这一新视角探索肝纤维化分子机制，为临床治疗肝纤维化提供新的理论和实验依据。

The regulatory role of long non-coding RNA (lncRNA) in liver fibrosis is not clear. In our previous studies, the expression of lncRNA4166 and its cis gene: heart and neural crest derivatives expressed transcript 2 (HAND2) increased, its target miRNA92a decreased in human primary hepatic stellate cells (HSC) and cirrhosis patients. It is concluded that they cooperate with HSC activation and liver fibrosis promotion. Then we explore the mechanism of overexpression or suppression genes in lncRNA4166-miRNA92a-HAND2 axis that regulate its downstream target signaling pathway in liver fibrosis and impact on HSC functions of activation, apoptosis in vitro. We also clarify the rule of inhibition lncRNA4166, HAND2 or derepression miRNA92a that reverse liver fibrosis in liver-specific knockout HAND2 mice and liver fibrosis rats induced by DEN or CCl4. Finally, the expression of these genes and their association with prognosis were observed in chronic liver disease of different causes. The results of the study will help us to explore the molecular mechanism of lncRNA4166 in liver fibrosis and provides a new theoretical and experimental basis for the clinical treatment of liver fibrosis.