胰岛素抵抗在非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）中扮演关键角色，西医对本病尚无特效药物。苓桂术甘汤作为传统经方在临床上被广泛应用于NAFLD的治疗中，疗效显著，但确切分子机制不明。前期研究发现肝细胞核因子1b（HNF1b）通过负调控DPP4/NOX1介导的超氧化物的产生，在控制肝脏甘油三酯稳态和胰岛素敏感性方面发挥重要作用。HNF1b的敲除增加了小鼠和肝细胞中的肝脏脂质含量以及诱导胰岛素抵抗。HNF1b高表达能够减轻高脂饮食小鼠的肝脏脂质含量以及减轻胰岛素抵抗。我们在临床上也发现苓桂术甘汤能够显著改善NAFLD患者胰岛素抵抗，降低血脂水平。基于此我们提出假说：苓桂术甘汤通过调控HNF1b/DPP4/NOX1通路逆转胰岛素抵抗，缓解NAFLD。预期结果将为阐明苓桂术甘汤作用机制，为非酒精性脂肪性肝病的中医药治疗提供新的思路。

Insulin resistance plays a key role in the mechanism of NAFLD. There is no specific drug in western medicine. As a classical Chinese herbal formula, Linggui Zhugan decoction (LGZG) is widely prescribed to treat NAFLD in clinical practice with significant effect. However, the exact molecular mechanism is unclear by far. Previous studies have shown that HNF1b can decrease the generation of superoxide mediated by DPP4 /NOX1 pathway through negative regulation. Therefore it plays an important role in controlling the steady state of triglyceride in liver and enhancing insulin sensitivity. HNF1b knockout can increase lipid content in the mouse liver and induce insulin resistance. HNF1b high-expression can reduce liver lipid content in high-fat-diet-induced mouse model and reduce insulin resistance. In clinic, we also find that LGZG can improve insulin resistance and lower lipid profile. Based on these studies, we propose the hypothesis that LGZG can reverse insulin resistance and ease NAFLD through HNF1b/DPP4/NOX1 pathway. The expected results can help us to illustrate the mechanisim of LGZG decoction and provide a new treatment for preventing and controlling NAFLD by traditional Chinese medicine.