基于高分辨UPLC/Q-TOF MS/MS检测技术的黄嘌呤氧化还原酶在NAFLD发生发展中作用机制及生物标志物研究

非酒精性脂肪肝病（NAFLD）是一种高发的代谢性疾病，可导致肝硬化、肝功能衰竭等严重后果。然而NAFLD的发病机制不明确，也无有效治疗药物，因此寻找生物标志物对NAFLD早期诊断和预防具有重要意义。黄嘌呤氧化还原酶（XOR）是嘌呤代谢的限速酶，与NAFLD等代谢性疾病密切相关。申请人前期在NAFLD动物模型中抑制XOR活性后发现血糖和糖化血清蛋白显著降低，提示XOR可能参与并加重了NAFLD的糖代谢紊乱。但是尚缺少XOR在NAFLD发病机制中作用的证据。本课题拟利用高分辨UPLC/Q-TOF MS/MS检测技术对NAFLD人群和大鼠模型进行血清代谢组学研究，筛选与XOR相关的生物标志物，进行代谢通路分析，验证生物标志物上游催化酶的表达情况，揭示XOR在NAFLD发展中的作用机制。本研究将为NAFLD的早期诊断提供卫生分析新策略，为NAFLD的治疗提供理论依据。

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disease that can lead to serious consequences such as cirrhosis and liver failure. However, the pathogenesis of NAFLD is unclear and there are no effective therapeutic drugs, so the search for biomarkers is important for the early diagnosis and prevention of NAFLD. Xanthine oxidoreductase (XOR) is the rate-limiting enzyme of purine metabolism, which is closely related to metabolic diseases such as NAFLD. We found a significant decrease in blood glucose and glycated serum protein after inhibiting XOR activity in an animal model of NAFLD, suggesting that XOR may be involved in and aggravate the disorder of glucose metabolism in NAFLD. However, evidence for the role of XOR in the pathogenesis of NAFLD is still lacking. In this study, we propose to use UPLC/Q-TOF MS/MS, a high-resolution assay technology, to perform serum metabolomics studies in NAFLD population and rat models, screen XOR-related biomarkers, perform metabolic pathway analysis, verify the expression of upstream catalase of biomarkers, and reveal the mechanism of XOR's role in the development of NAFLD. This study will provide a new strategy for health analysis for the early diagnosis of NAFLD and provide a theoretical basis for the treatment of NAFLD.