浙江医学2023，Vol.45Issue(24)：2600-2604,后插3-后插4,7.DOI:10.12056/j.issn.1006-2785.2023.45.24.2023-1165
高脂饮食诱导下小鼠肾脏组织蛋白质组学研究
Differentially expressed proteins in mouse kidney tissue induced by high-fat diet
摘要
Abstract
Objective To investigate the differentially expressed proteins(DEPs)in mouse kidney tissue induced by high-fat diet.Methods Twenty-two male C57BL/6 mice were divided into a control group(n=11)and a high-fat group(n=11);two groups were fed with normal diet(fat energy accounting for 10％)or high-fat diet(fat energy accounting for 60％)for 24 weeks,respectively.After the mice were euthanized,blood samples were collected from the eye socket,and the serum levels of total cholesterol(TC),triglycerides(TG),blood glucose(BG),serum creatinine(Scr),burea nitrogen(BUN)were measured.Kidney tissue samples were subjected to HE staining,periodic acid-Schiff(PAS)staining,and electron microscopy to observe pathological changes.Total proteins were extracted from the kidney tissue and detected by high-performance liquid chromatography.The 4D label-free quantitative proteomic technique was employed,and the differential proteins were defined as those with a fold change＞1.5(upregulated)or＜1/1.5(downregulated).DEPs were screened,and functional annotation and enrichment analysis were performed.Core proteins were selected through protein interaction network analysis.Results The weight,and serum TC,TG,BG,Scr,and BUN levels in the high-fat group were significantly higher than those in the control group(all P＜0.05).Compared to the control group,the high-fat group exhibited slightly larger glomerular volume,showing a slight increase of mesangial cells and matrix segments,thickening of Bowman's capsule wall,and significant vacuolar degeneration of renal tubular epithelial cells.Electron microscopy revealed fusion of foot processes in the high-fat group mice,noticeable swelling and deformation of mitochondria of varying sizes,increased lysosome-like structures,and the presence of autophagic bodies.A total of 93 DEPs were identified between the two groups,including 49 upregulated proteins and 44 downregulated proteins in high-fat group.Functional enrichment and pathway bioinformatics analysis indicated that DEPs were mainly involved in lipid and carbohydrate transport and metabolic pathways.Significantly enriched pathways included peroxisome and lysosome-related pathways,as well as primary bile acid biosynthesis,steroid hormone biosynthesis,and the renin-angiotensin system.Protein interaction network analysis revealed that proteins closely associated with the high-fat-induced renal damage included Acox2,ApoA4,Phyh,Amacr,ApoE,Gnpat,and Tysnd1.Conclusion High-fat diet can induce changes in the renal proteome,primarily involving peroxisome-related and matrix enzyme-related metabolic pathways,leading to the renal toxicity in mice.关键词
高脂饮食/肾脏/蛋白质组学/过氧化物酶体Key words
High-fat diet/Kidney/Proteomics/Peroxisome引用本文复制引用
陈智鸿,王林,黄津华..高脂饮食诱导下小鼠肾脏组织蛋白质组学研究[J].浙江医学,2023,45(24):2600-2604,后插3-后插4,7.基金项目
复旦大学附属中山医院厦门医院孵化课题(2020ZSXMYS04) （2020ZSXMYS04）
厦门市医疗卫生指导性项目(3502Z20224ZD1080) （3502Z20224ZD1080）
