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 UL 122 transgenic model mice

作　　者：周晓琼 张现娟 王斌[1] ZHOU Xiaoqiong;ZHANG Xianjuan;WANG Bin(School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院,山东青岛266071

出　　处：《精准医学杂志》2024年第1期15-20,共6页Journal of Precision Medicine

基　　金：国家重点研发计划项目(2018YFA0900802)。

摘　　要：目的探讨人巨细胞病毒即刻早期蛋白2(HCMV-IE2)对果糖诱导的UL 122转基因模型小鼠肝脏脂肪变性的影响。方法构建UL 122转基因小鼠模型作为实验组,以同龄野生型小鼠作为对照组,以60%的高果糖饲料饲养8周,监测小鼠体质量、血糖的变化,并行葡萄糖耐量实验和胰岛素耐量实验后处死小鼠,测定小鼠血清中丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平以及肝脏组织中三酰甘油(TG)和总胆固醇(TC)水平;取小鼠肝脏组织行HE染色和油红O染色进行组织病理学观察;流式细胞术检测肝脏组织中巨噬细胞极化情况;RT-qPCR和Western blot方法检测肝脏脂质合成相关基因mRNA和蛋白的表达水平。结果与对照组相比,实验组小鼠体质量和空腹血糖水平明显升高(F=12.78~100.05,P<0.05),出现了明显的糖耐量异常和胰岛素抵抗,GTT和ITT曲线下面积明显增大(t=3.25、4.70,P<0.05),血清中ALT、AST水平和肝脏中TG、TC水平显著增高(t=4.52~13.12,P<0.05)。实验组小鼠肝脏组织中M1型巨噬细胞比例明显升高,而M2型巨噬细胞比例明显下降(t=4.81~12.12,P<0.05),肝脏脂质合成基因SREBP1c、ACC 1、FAS和CD 36的mRNA和蛋白表达水平均明显升高(t=3.54~9.96,P<0.05)。结论HCMV-IE2可能通过诱导肝脏中巨噬细胞M1型极化影响肝脏脂质代谢平衡,从而促进果糖诱导的非酒精性脂肪肝的进展。Objective To investigate the effect of human cytomegalovirus immediate-early protein 2(HCMV-IE2)on fructose-induced hepatic steatosis in UL 122 transgenic model mice.Methods The UL 122 transgenic mice were established as experimental 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 tissue 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 expression 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,ACC 1,FAS,and CD 36 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 

分 类 号：R575.5[医药卫生—消化系统]