固醇调节元件结合蛋白（SREBP）在非酒精性脂肪性肝病中的作用机制及治疗靶点

Abstract

非酒精性脂肪性肝病 (NAFLD) 已成为全球范围内最常见的肝脏疾病，是肝癌发展的重要风险因素。然而，NAFLD的发病机制目前仍未被完全阐明，且尚无特异性的有效治疗措施。固醇调节元件结合蛋白 (SREBP) 是一类重要的核转录因子，主要通过激活胆固醇、脂肪酸和甘油三酯合成及摄取的相关基因来维持体内脂质代谢的平衡，是治疗代谢性疾病的靶点。本文对SREBP参与NAFLD发病机制的最新进展以及SREBP靶向治疗NAFLD的最新证据进行综述。值得注意的是，最近研究发现SREBP抑制与自噬受损共同引发肝损伤。因此，过度抑制脂肪生成对NAFLD的治疗可能起反作用。总体而言，SREBP是一个具有广阔前景的NAFLD治疗靶点，其对脂质代谢的分子机制受多种因素的调控，而这些因素正在被深入探索和分析，对NAFLD治疗具有重要的临床意义。

Alternate abstract:

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma. However, the pathogenesis of NAFLD remains unclear, and there is still a lack of specific treatment measures. Sterol regulatory element-binding proteins (SREBP) are an important nuclear transcription factor, which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol, fatty acids, and triglycerides, and therefore, SREBP are a target for the treatment of metabolic diseases. This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD. It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage. Therefore, excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD. In conclusion, SREBP is a promising therapeutic target for NAFLD; the molecular mechanism of SREBP in lipid metabolism is regulated by many factors, and these factors are being deeply explored and analyzed, which has an important clinical significance for the treatment of NAFLD.