Role of lipid raft on palmitic acid induced-cell death in primary-cultured mouse hepatocytes

过量的饱和游离脂肪酸（sFFA）导致肝脏脂肪变性和损伤，这部分解释了非酒精性脂肪性肝炎（NASH）的发病机制。脂筏是细胞膜上含有高浓度胆固醇和鞘糖脂的亚结构域，参与多种细胞信号转导过程。在这项研究中，我们研究了游离FFA对脂质筏结构形成的影响，以及氧化应激诱导的离体肝细胞损伤。PA在离体肝细胞中增强脂质蓄积和对氧化应激诱导的细胞死亡的敏感性。这一过程似乎与脂筏的聚集密切相关，通过CHOX阻断这一现象可防止PA预处理肝细胞中的氧化性细胞杀伤。脂筏可能在脂肪肝细胞氧化应激相关的细胞损伤中起关键作用，这为NASH的预防和治疗提供了潜在的靶点。

Excessive saturated free fatty acid (sFFA) causes hepatic steatosis and injury, which explains in part the pathogenesis of nonalcoholic steatohepatitis (NASH). Lipid raft, the plasma membrane subdomain that contains high concentration of cholesterol and glycosphingolipids, is involved in a variety of cellular signal transduction processes. In this study, we investigated the impact of sFFA on structure formation of lipid raft, and oxidative stress-induced cell injury in isolated hepatocytes. PA elicits lipid accumulation and sensitization to oxidative stress-induced cell death in isolated hepatocytes. This process appears to be closely related to the clusterization of lipid raft, and blockade of this phenomenon by CHOX prevents oxidative cell killing in PA-pretreated hepatocytes. Lipid raft most likely plays a pivotal role in oxidative stress-related cell injury in fat-loaded hepatocytes, which provides a potential uniquetarget for the prevention and treatment of NASH.