高尿酸血症与糖尿病、高脂血症、脂肪肝等代谢性疾病的发生发展密切相关。本文旨在建立稳定的糖脂代谢紊乱小鼠模型，并应用筛选出的具有降尿酸活性的化合物，探究抗高尿酸血症化合物对糖脂代谢紊乱和非酒精性脂肪肝的改善作用。

应用高脂饲料饮食长期诱导建立具有胰岛素抵抗、糖脂代谢紊乱、和肝脂堆积等特点的肥胖小鼠模型。挑选DIO模型小鼠，给药5周，以禁食血糖、口服葡萄糖耐量测试评价糖代谢状态；以血清总胆固醇、血清高密度脂蛋白胆固醇、血清低密度脂蛋白胆固醇、和血甘油三酯评价血脂状态；以肝脏指数、肝脏TG含量评价肝脏的脂肪堆积情况；以空腹血胰岛素水平、和胰岛素抵抗指数评价动物全身胰岛素敏感性。结果显示，化合物YDA-4-43显示明显改善糖代谢紊乱、血脂紊乱、肝脂堆积、以及胰岛素抵抗的作用；化合物TAZ-3-19对血脂紊乱、肝脂堆积和胰岛素抵抗具有一定的改善作用； 化合物wyc-2034则仅对血TG和胰岛素抵抗显示一定的改善作用；化合物wyc-1804对上述代谢性病变未见明显作用。

综上所述，本研究应用高脂饲料诱导DIO模型小鼠，发现具有显著抗高尿酸血症的化合物可在一定程度上显示改善糖脂代谢紊乱和胰岛素抵抗的作用，为治疗高尿酸血症合并糖脂代谢紊乱提供新思路。

Hyperuricemia is related to the development of metabolic diseases closely, including diabetes, hyperlipidemia, non-alcoholic fatty liver disease (NAFLD)，and so on. The purpose of this study is to set up a mouse model with steady glycolipid metabolic disorders, and investigate the effects of compounds with the anti-hyperuricemia activity on improving glycolipid metabolic disorders.

Diet-induced obesity (DIO) mouse model with insulin resistance (IR), glycolipid metabolic disorders was established by long-term high-fat diet. Drugs were consecutively administrated for five weeks. The glucose metabolism was evaluated by fasting blood glucose and oral glucose tolerance test (OGTT); total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol，triglyceride evaluate blood lipid level;  liver fat accumulation was assessed by liver index, and liver TG content; the insulin sensitivity was evaluated by fasting blood insulin and HOMA-IR, respectively. The results showed that compound YDA-4-43 improved glucose metabolic disorder, blood lipid disorder, liver fat accumulation and insulin resistance, respectively. Compound TAZ-3-19 has certain improvements on blood lipid disorders and insulin resistance. Compound wyc-2034 just improved blood TG, and insulin resistance. The effects of compound wyc-1804 on the above metabolic disorders did not be observed.

In summary, in the diet-induced DIO mice, compounds with uric acid-lowering active might improve on glycolipid metabolic disorders and insulin resistance. This study provided new insight for the treatment of hyperuricemia complicated with glycolipid metabolic disorders.