脾虚血瘀为高脂饮食下非酒精性脂肪肝（NAFLD）中医关键病机之一。我们的前期研究证明以健脾祛瘀为治法拟定的去脂软肝方可通过激活脂质氧化、降低炎症反应有效治疗NAFLD。由于过氧化物酶体增殖激活受体α（PPARα）激活后调控下游脂质代谢关键基因表达，可减少肝脏脂质沉积；活化的NF-κB诱导激酶（NIK）则通过NF-κB通路加剧脂质过氧化及炎症反应。NIK/PPARa间存在相互制约关系，在肝脏脂质代谢稳态失衡诱发NAFLD中具有重要作用。为此提出去脂软肝方可通过调节NIK/PPARα互作影响下游关键基因表达，维持肝脏脂质代谢稳态防治NAFLD的科学假说。本研究拟复制高脂诱导NAFLD大鼠模型和L0-2细胞模型，探讨去脂软肝方对NIK/PPARα及下游基因表达的影响，在转染报告基因的HepG2细胞中探明其调节NIK/PPARα互作机理，在动物整体和细胞分子水平阐释该方防治NAFLD分子机制。

Spleen deficiency and blood stasis is one of the key pathogenesis of non-alcoholic fatty liver disease (NAFLD) caused by high-fat diet in traditional Chinese medicine. Qu Zhi Ruan Gan (QZRG) Formula which aims to invigorate spleen and remove stasis, shows significantly positive effect on prevention and treatment of NAFLD though activating lipid oxidation, reducing blood lipid and alleviating the inflammation by our previous studies. Since peroxisome proliferator-activated receptor alpha (PPARα) regulates the expression of key lipid metabolism genes in downstream, it can reduce liver lipid deposition. Meanwhile activated NF-κB-inducing kinase (NIK) enhances lipid peroxidation and inflammation through the NF-κB pathway. NIK/PPARα interacted and influenced with each other, which plays a significant role in NAFLD induced by lipid homeostasis imbalance in liver. Based on all above backgrounds, we propose the hypothesis that the QZRG Formula can ameliorate and sustain homeostasis of liver lipid metabolism in NAFLD rats effectively though regulating NIK/PPARα interaction. By moderating the NIK/PPARα interaction, it can affect downstream genes expression including lipid metabolism and inflammation. In order to verify the hypothesis, this study will be replicating the high-fat diet induced NAFLD rat model and culturing high FFA L0-2 cell line to validate the effects of QZRG Formula on NIK/PPARα and downstream gene expression. Meanwhile, QZRQ Formula mediating the mechanism of NIK/PPARαinteraction will be validated in HepG2 cell line transfected with reporter gene in vitro. This study aims at illustrating the molecular mechanism of prevention and treatment of NAFLD by QZRG Formula and will provide the theory basis of multi-link and multi-level treatments of NAFLD by Chinese medicine Formula.