1.贵州中医药大学,贵阳 550025;2.贵州中医药大学第二附属医院,贵阳 550003
1. Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China. 2. the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550003
目的 应用蛋白质组学方法分析酒精性脂肪肝(alcoholic fatty liver disease,AFLD)小鼠肝组织蛋白表达谱变化及白藜芦醇干预影响。 方法 采用 NIAAA 法制备 C57BL/ 6J 小鼠 AFLD 模型,连续 9 d 灌胃给予白藜芦醇(400 mg / kg)干预。 采用 4D 非标定量蛋白质组方法对各实验组小鼠肝组织中的蛋白质进行鉴定和定量。 以同时满足倍数变化≥1. 5 或≤0. 67,且 P<0. 05 的条件对正常对照组与 AFLD 组、AFLD 组与白藜芦醇干预组,正常 对照组与白藜芦醇等 3 个比较组中显著上调或下调差异表达蛋白进行筛选,然后进行差异表达蛋白的 GO 分类、 KEGG 通路富集和蛋白质网络互作分析。 结果 分别鉴定和定量到 4513、3763 个蛋白质,筛选出 1228 个差异表达 蛋白质和 11 个差异共表达蛋白质。与对照组比较(P<0. 05),AFLD 组分别有 370、324 个蛋白质显著下调和上调, 白藜芦醇干预组分别有 40、43 个蛋白质显著上调和下调;与 AFLD 组比较(P<0. 05),白藜芦醇干预组分别有 224、 227 个蛋白质显著上调和下调。 1228 个差异表达蛋白质分别涉及 GO 注释的 40 个生物学过程、36 个细胞组成、38 个分子功能和 45 条 KEGG 通路,11 个差异共表达蛋白经 GO、KEGG 及蛋白质质网络互作分析,其中 9 个差异共表 达蛋白质涉及 9 种分子功能、5 个差异共表达蛋白质涉及 5 条信号通路,4 个差异共表达蛋白质发生了相互作用。 结论 慢性酒精摄入后小鼠肝组织蛋白表达谱发生了显著变化,硫转移酶家族胞浆 1B 成员 1( sulfotransferase family cytosolic 1B member 1, Sult1b1)、载脂蛋白 A-IV( apolipoprotein A-IV,Apoa4)、甘油-3-磷酸酰基转移酶 3 (glycerol-3-phosphate acyltransferase 3,Gpat3)、环氧化物水解酶 1( epoxide hydrolase 1,Ephx1)等 4 种蛋白质表达水平变化与 AFLD 的发生和白藜芦醇的 AFLD 干预作用具有密切关系。
Objective Proteomics were used to analyze changes in the liver protein expression profile of AFLD mice and the effect of resveratrol treatment. Methods The AFLD model of C57BL/ 6J mice was prepared by NIAAA method, and resveratol(400 mg / kg)was administered orally for 9 days. Proteins in the liver tissues were quantified by the 4D non-standard quantitative proteomic method . Under conditions of multiple changes ≥1. 5 or ≤0. 67 and P< 0. 05, significantly up- or down-regulated differentially expressed proteins in three comparison groups were screened. GO classification, KEGG pathway enrichment, and protein network interaction analysis of differentially expressed proteins were carried out. Results Totals of 4513 and 3763 proteins were identified and quantified, respectively, and 1228 differentially expressed proteins and 11 differentially coexpressed proteins were screened. Compared with the control group (P<0. 05), 370 and 324 proteins were significantly down- and up-regulated in the AFLD group. Compared with the AFLD group (P< 0.05), 224 and 227 proteins were significantly up- and down-regulated, respectively, in the resveratrol treatment group. A total of 1228 differentially expressed proteins were involved in 40 biological processes, 36 cellular components, 38 molecular functions, and 45 KEGG pathways annotated by GO classification. A total of 11 differentially coexpressed proteins were screened and found to be related to 9 molecular functions and 5 signaling pathways, of which 4 differentially coexpressed proteins interacted. Conclusions After chronic alcohol intake, the protein expression profile of mouse liver tissue changes significantly. The changes in expression of Sult1b1 (sulfotransferase family cytosolic 1B member 1), Apoa4 (apolipoprotein A-IV), Gpat3 ( glycerol-3-phosphate acyltransferase 3), and Ephx1 ( epoxide hydrolase 1) were closely related to AFLD occurrence and the therapeutic effect of resveratrol on AFLD.
韩 敏,易 旭,游绍伟.酒精性脂肪肝小鼠肝组织蛋白表达谱检测及白藜芦醇干预作用机制的探讨[J].中国比较医学杂志,2023,33(1):16~25.复制