癌变·畸变·突变2025，Vol.37Issue(4)：319-323,329,6.DOI:10.3969/j.issn.1004-616x.2025.04.016
铁超载加重非酒精性脂肪肝病过程中线粒体自噬的作用及其机制
The role and mechanism of mitochondrial autophagy in the process of iron overload aggravating nonalcoholic fatty liver disease
摘要
Abstract
OBJECTIVE:To establish a mouse model of non-alcoholic fatty liver disease(NAFLD),and to study the role and mechanism of mitochondrial autophagy in the pathogenesis of NAFLD aggravated by iron overload.METHODS:Seventy-two male C57BL/6 mice were randomly divided into control group,high iron group,high fat group,and high iron plus high fat group.The mice were fed continuously until the end of the experiment,with 18 mice in each group.The mice were sacrificed at the 8th and 12th weeks,respectively,and were subjected to blood biochemical indexes,liver histopathology;and protein expression levels of mitochondrial dynamicsrelated factors OPA1 and DRP1,autophagy and mitochondrial autophagy-related factors PINK1,Parkin which were detected by Western blot and the mRNA levels of PINK1 and Parkin were detected by real-time quantitative PCR(RT-qPCR).RESULTS:Compared with the control group,a simple high-fat diet significantly increased the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)(P<0.05),promoted hepatic steatosis,reduced the expression of mitochondrial fusion proteins OPA1,increased the expression of mitochondrial fission proteins DRP1,and reduced the expression levels of mitochondrial autophagy-related proteins and genes PINK1 and Parkin(P<0.05).The high-speed rail group upregulated the mRNA expression levels of mitochondrial related factor OPA1 protein and Parkin at weeks 8and 12(P<0.05).The combined effect of high-fat and high iron diet further increased serum TG and ALT levels,exacerbated liver damage(P<0.05),and affected expressions of mitochondrial autophagy-related proteins PINK1 and Parkin,as well as genes PINK and Parkin.CONCLUSION:High-fat diets successfully induced the establishment of a NAFLD modeling in mice.Iron overload promoted elevation of blood lipids and hepatic lipid deposition during the occurrence and development of NAFLD,aggravated liver function and mitochondrial damage,thereby promoted the progression of NAFLD.关键词
非酒精性脂肪肝/自噬/线粒体自噬/炎症/铁超载Key words
nonalcoholic fatty liver disease/autophagy/mitochondrial autophagy/inflammation/iron overloda分类
医药卫生引用本文复制引用
陈怡如,王丽,武鑫悦,赵艳..铁超载加重非酒精性脂肪肝病过程中线粒体自噬的作用及其机制[J].癌变·畸变·突变,2025,37(4):319-323,329,6.基金项目
黑龙江省自然科学基金(LH2021H061) （LH2021H061）
