肠-肝免疫轴在非酒精性脂肪性肝炎发病中的作用

Role of gut-liver-immune axis in the pathogenesis of nonalcoholic steatohepatitis

非酒精性脂肪性肝病(NAFLD)已成为全球最常见的慢性肝病,是肝硬化、肝癌和多种肝外慢性疾病的重要危险因素,目前仍缺乏有效的治疗药物。肝脏炎症是NAFLD进展的关键驱动因素,因而调控肝脏炎症有望为延缓和逆转非酒精性脂肪性肝炎(NASH)进展提供潜在手段。研究发现,肠-肝免疫轴在NASH进展中扮演了重要角色。肠道菌群可利用其代谢物诱发糖脂毒性、氧化应激和肠道屏障损伤,而细菌组分如脂多糖、肽聚糖、细菌DNA和胞外囊泡等可经由受损的肠道屏障转位进入肝脏,引发免疫细胞过度激活,进而加剧肝脏炎症反应和促进NASH进展。现围绕肠-肝免疫轴解析肠道菌群介导的肝脏免疫和其在NASH发生、发展中的作用机制,为研发NASH治疗新策略奠定理论基础。

Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease in the world.Liver cirrhosis,liver cancer and a variety of extrahepatic chronic diseases are important risk factors for NAFLD.Currently,there is still a lack of effective therapeutic drugs.Liver inflammation is a key driving factor for the progression of NAFLD,so regulating liver inflammation may provide a potential means to delay and reverse the progression of nonalcoholic steatohepatitis(NASH).Studies have found that the gut-liver-immune axis plays an important role in the progression of NASH.Gut microbiota can use its metabolites to induce glycolipid toxicity,oxidative stress and intestinal barrier damage,while bacterial components such as lipopolysaccharides,peptidoglycans,bacterial DNA and extracellular vesicles can translocate into the liver through the damaged intestinal barrier,causing excessive activation of immune cells,thus aggravating liver inflammation and promoting the progress of NASH.This paper focuses on the gut-liver-immune axis to analyze the gut microbiota mediated liver immunity and its mechanism in the occurrence and development of NASH,so as to lay a theoretical foundation for the research and development of new therapeutic strategies for NASH.