单核细胞来源的巨噬细胞(MoMF)在肝纤维化中具有关键作用，而VEGF-C参与MoMF趋化。我们发现主成份为柚皮苷的胡柚皮黄酮能有效缓解非酒精性脂肪性肝纤维化，且网络药理学预测其主要靶点为VEGF-C。文献分析发现，柚皮苷可分别作用于饥饿素受体（GHSR）和AMPK/SREBP1，而软件预测SREBP1为VEGF-C的转录因子。我们假说：柚皮苷结合GHSR，磷酸化AMPK，抑制下游SREBP1介导的VEGF-C转录，继而抑制其对外周Ly6Chi单核细胞招募，缓解肝纤维化。拟采用肝特异性敲除VEGF-C小鼠建立NASH模型，明确VEGF-C对Ly6Chi单核细胞向肝脏趋化等事件的作用；结合柚皮苷处理模型小鼠及体外实验，从GHSR/AMPK/SREBP-1通路介导VEGF-C转录角度，阐明柚皮苷抗肝纤维化的分子机制，为柚皮苷等黄酮类药物防治NASH提供理论依据和优化策略。

Monocyte-derived macrophages (MoMF) play an important role in liver fibrosis. Vascular endothelial growth factor-C (VEGF-C) is involved in fibrosis and is chemotactic for MoMF. We found that Pure total flavonoids from Citrus (PTFC), of which the main component is naringin, effectively reduced the symptoms of nonalcoholic fatty liver fibrosis. VEGF-C was predicted as the key target of PTFC via network pharmacology analysis. Studies showed that naringin functions on both ghrelin receptor (GHSR) and AMPK/SREBP1 signaling. SREBP1 is predicted as a transcription factor of VEGF-C. To this end, we hypothesize that naringin binds GHSR and mediates AMPK phosphorylation and activation. This in turn suppresses SREBP1-mediated VEGF-C transcription, followed by reduced Ly6Chi monocytes recruitment and liver fibrosis. To fulfill this hypothesis, by using the liver-specific knockout VEGF-C mice to establish a NASH model, we first try to determine the chemotactic effects of VEGF-C on Ly6Chi monocytes trafficking to liver and other relative major events; by using naringin to treat model mice and in vitro experiments, we try to elucidate the molecular mechanism of naringin inhibiting liver fibrosis from the aspect of GHSR/AMPK/SREBP-1 signaling pathway on VEGF-C transcription. This research may provide theoretical basis and optimization strategy for prevention and treatment of NASH based on flavonoids such as naringin.