胆固醇代谢与非酒精性脂肪性肝炎  

Cholesterol metabolism and non-alcoholic steatohepatitis

作　　者：马振增[1] 陆伦根[1] 

机构地区：[1]上海交通大学附属第一人民医院消化科,200080

出　　处：《中华肝脏病杂志》2016年第8期623-627,共5页Chinese Journal of Hepatology

摘　　要：非酒精性脂肪性肝病（NAFLD）的疾病谱包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎（NASH）及其相关肝硬化和肝细胞癌，其严重类型是NASH。在全世界范围内，NAFLD发病率逐年上升，是慢性肝病的常见原因且缺乏有效的治疗措施。NASH发病机制尚不十分清楚，以前多应用两次打击学说解释NASH发病机制；随着研究进展，发现胆固醇代谢与NASH的发病及其严重程度密切相关，目前这一观点受到挑战，提出了多种平行打击的假说。胆固醇可以通过遗传因素、影响膜流动性和膜蛋白的功能、诱导未折叠蛋白反应、产生毒性氧化型胆固醇、游离胆固醇激活枯否细胞及星状细胞产生炎症因子及胶原蛋白、胆固醇结晶及其冠状结构的形成损害肝细胞和活化枯否细胞等过程来加重肝细胞的损伤，从而在NASH的发病过程中加速NASH的发病和加重NASH的临床表现，现就胆固醇代谢与NASH发病机制之间的关系进行综述。The disease spectrum of non-alcoholic fatty liver disease （NAFLD） includes non-alcoholic simple fatty liver （NAFL） and non-alcoholic steatohepatitis （NASH）, as well as liver cirrhosis and hepatocellular carcinoma, with the most serious type being NASH. The morbidity of NAFLD is seeing an increase year by year in the world, and it is a common cause of chronic hepatic disease and lacks effective treatment. The pathogenesis of NASH is still unknown, and the ＂two-hit＂ hypothesis was used to explain the mechanism of NASH. Recent research has found that cholesterol metabolism is closely related to the pathogenesis and severity of NASH. The validity of the ＂two-hit＂ hypothesis has been recently challenged, which gives rise to ＂multi-parallel hit＂ hypothesis. Cholesterol affects membrane fluidity and membrane protein function through genetic factors, and it can also induce unfolded protein response, and generate toxic oxysterol. Free cholesterol can activate hepatic Kupffer and stellate cells to produce inflammatory cytokines and collagen. The formation of cholesterol crystallization and crown-like structures can damage liver cells and activate Kupffer cells. The above processes can all aggravate liver damage, thus accelerating the development and making the clinical manifestations of NASH even worse. In the present review we summarize the association between cholesterol metabolism and pathogenesis of NASH.

关 键 词：胆固醇代谢 肝炎 脂肪胜 非酒精性 发病机制 遗传因素 未折叠蛋白反应 毒性氧化型胆固醇 冠状结构 枯否细胞 星状细胞 

分 类 号：R575.1[医药卫生—消化系统]