非酒精性脂肪性肝炎（NASH）是非酒精性脂肪肝病（NAFLD）的一种进行性形式，可引起肝硬化和肝细胞性肝癌。铁是体内必需的微量元素，但是过多的铁会导致组织损伤和功能障碍。NASH患者常常出现铁超负荷现象，并且肝脏中积累的铁量与NASH的组织学严重程度呈正相关。铁依赖性细胞死亡的一种新形式——铁过量引起的镁铁蛋白质，是由于脂质过氧化和氧化应激的积聚引起的，并与NASH相关。此外，镁铁蛋白质与细胞自我降解过程——嗜废细胞杀伤作用密切相关。虽然嗜废细胞杀伤作用具有许多有益的效果，但它也可能对机体有害，比如引起镁铁蛋白质。目前尚不清楚铁超负荷是否通过嗜废细胞杀伤作用加重了NASH的病情。本研究旨在确定铁超负荷通过嗜废细胞杀伤作用引起着镁铁蛋白质并加重NASH的机制。将特约高血压倾向于中风的自发性高血压大鼠（SHRSP5/Dmcr）分为两组，并喂养高脂高胆固醇（HFC）饮食八周。针对铁组，还注射了铁葡萄糖酸盐。进行了血液分析、组织学染色、钙酶活性测定、定量逆转录聚合酶链反应（RT-PCR）、免疫荧光染色和电子显微镜检查等实验。结果表明，铁超负荷通过转录因子EB（TFEB）的核转位促进了嗜废细胞杀伤作用，并引起镁铁蛋白质（即镁铁蛋白质的自噬降解）。此外，HFC饮食还引起了脂肪滴泡的嗜废细胞杀伤作用（即脂肪滴泡的自噬降解）。铁组还表现出促进的镁铁蛋白质和加重的肝炎和纤维化。总之，铁超负荷通过加速镁铁蛋白质和脂肪滴泡的自噬降解，加重了NASH的病理变化。这些结果表明，抑制自噬和镁铁蛋白质具有治疗NASH的潜力。

Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that causes cirrhosis and hepatocellular carcinoma. Iron is an essential trace element in the body; however, excess iron can cause tissue damage and dysfunction. Iron overload is often observed in patients with NASH, and the amount of iron accumulated in the liver positively correlates with the histological severity of NASH. Ferroptosis, a novel form of iron-dependent cell death, is caused by the accumulation of lipid peroxidation and oxidative stress and is related to NASH. In addition, ferroptosis is closely related to autophagy, an intracellular self-degradation process. Although autophagy has many beneficial effects, it may also be harmful to the organism, for example, inducing ferroptosis. It is unclear whether iron overload aggravates NASH via autophagy. The aim of this research is to determine the mechanism by which iron overload induces ferroptosis via autophagy and aggravates NASH. Stroke-prone spontaneously hypertensive rats (SHRSP5/Dmcr) were divided into two groups and fed a high-fat and high-cholesterol (HFC) diet for eight weeks. Iron dextran was administered to the Fe group in addition to the HFC diet. Blood analysis, histological staining, calcineurin activity assay, quantitative reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence staining, and electron microscopy were performed. The results showed that iron overload promoted autophagy via nuclear translocation of transcription factor EB (TFEB) and induced ferritinophagy, which is the autophagic degradation of ferritin. In addition, the HFC diet induced lipophagy, the autophagic degradation of lipid droplets. The Fe group also exhibited promoted ferroptosis and aggravated hepatic inflammation and fibrosis. In conclusion, iron overload accelerates ferritinophagy and lipophagy, aggravating NASH pathology via ferroptosis. These findings indicate the therapeutic potential of inhibiting autophagy and ferroptosis for treating NASH.