精准医学杂志2024，Vol.39Issue(1)：15-20,6.DOI:10.13362/j.jpmed.202401004
HCMV-IE2对果糖诱导的UL122转基因模型小鼠肝脏脂肪变性的影响
Effect of human cytomegalovirus immediate-early protein 2 on hepatic steatosis induced by fructose in UL122 transgenic model mice
摘要
Abstract
Objective To investigate the effect of human cytomegalovirus immediate-early protein 2(HCMV-IE2)on fructose-induced hepatic steatosis in UL122 transgenic model mice.Methods The UL122 transgenic mice were established as ex-perimental group,and age-matched wild-type mice were established as control group.The mice were fed with high-fructose(60%)diet for 8 weeks,and the changes in body weight and blood glucose were monitored.After the glucose tolerance test and the insulin tolerance test were performed,the mice were sacrificed,and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured,as well as the levels of triglyceride(TG)and total cholesterol(TC)in the liver.Liver tis-sue was collected,and HE staining and oil red O staining were used to observe histopathological changes;flow cytometry was used to observe macrophage polarization in the liver;RT-qPCR and Western blot were used to measure the mRNA and protein expres-sion levels of lipid synthesis-related genes in the liver.Results Compared with the control group,the experimental group had significant increases in body weight and fasting blood glucose level(F=12.78-100.05,P＜0.05)and significantly impaired glucose tolerance and insulin resistance,with significant increases in the area under the GTT and ITT curves(t=3.25,4.70,P＜0.05).There were significant increases in the serum levels of ALT and AST and the levels of TG and TC in the liver(t=4.52-13.12,P＜0.05).The experimental group had a significant increase in the proportion of M1-type macrophages and a significant reduction in the proportion of M2-type macrophages in liver tissue(t=4.81-12.12,P＜0.05),as well as significant increases in the mRNA and protein expression levels of the lipid synthesis genes SREBP1c,ACC1,FAS,and CD36 in the liver(t=3.54-9.96,P＜0.05).Conclusion HCMV-IE2 affects the balance of liver lipid metabolism by inducing M1 polarization of macrophages in the liver,thereby promoting the progression of fructose-induced nonalcoholic fatty liver disease.关键词
非酒精性脂肪性肝病/果糖/小鼠,转基因/即早蛋白质类/葡糖耐受不良/胰岛素抵抗/巨噬细胞Key words
Non-alcoholic fatty liver disease/Fructose/Mice,transgenic/Immediate-early proteins/Glucose intole-rance/Insulin resistance/Macrophages分类
医药卫生引用本文复制引用
周晓琼,张现娟,王斌..HCMV-IE2对果糖诱导的UL122转基因模型小鼠肝脏脂肪变性的影响[J].精准医学杂志,2024,39(1):15-20,6.基金项目
国家重点研发计划项目(2018YFA0900802) （2018YFA0900802）
