中国免疫学杂志2025，Vol.41Issue(4)：885-892,8.DOI:10.3969/j.issn.1000-484X.2025.04.019
LncRNA MEG3调节miR-181b-5p/FOXP1轴对非酒精性脂肪性肝病小鼠的作用机制研究
Mechanism of LncRNA MEG3 on mice with non-alcoholic fatty liver disease by regulating miR-181b-5p/FOXP1 axis
摘要
Abstract
Objective:To investigate the mechanism of long non-coding RNA maternally expressed gene 3(LncRNA MEG3)on mice with non-alcoholic fatty liver disease(NAFLD)by regulating the miR-181b-5p/forkhead box protein P1(FOXP1)axis.Methods:NAFLD model was established in C57BL/6J mice by feeding high-fat diet for 12 weeks,which were randomly divided into NAFLD model group(tail vein injection of normal saline),LncRNA MEG3 overexpression group(tail vein injection of LncRNA MEG3 overex-pression plasmid),LncRNA MEG3 overexpression+miR-181b-5p mimics group(tail vein injection of LncRNA MEG3 overexpressed plasmid and miR-181b-5p mimics)and negative control group(tail vein injection of empty plasmid and miR-181b-5p mimics negative control),with 10 mice in each group.Another 10 mice were fed with common diet for 12 weeks as normal control group(tail vein injection of normal saline).Each group of mice was treated for 2 weeks,twice a week.Levels of serum lipid metabolism indexes triglyce-ride(TG),total cholesterol(TC),free fatty acid(FFA)and liver function indexes alanine aminotransferase(ALT),aspartate amino-transferase(AST)were measured by automatic biochemical analyzer;liver coefficient of mice in each group was measured;pathologi-cal morphology of liver tissue of mice in each group was detected by HE staining;levels of IL-6 and IL-18 in serum and liver tissue of mice in each group were measured by ELISA;expressions of LncRNA MEG3 and miR-181b-5p in liver tissues of mice in each group were detected by RT-qPCR;expression of FOXP1 in liver tissues of mice in each group was detected by RT-qPCR and Western blot.Targeting regulation of miR-181b-5p and LncRNA MEG3,and targeting regulation of FOXP1 and miR-181b-5p in mice liver paren-chyma cells were detected by double luciferase reporter gene assay.Results:Compared with normol control group,severe pathological injury occurred in liver tissue of mice in NAFLD model group,expressions of LncRNA MEG3,FOXP1 mRNA and protein in liver tissue were decreased obviously(P<0.05),levels of TG,TC,FFA,ALT and AST,liver coefficient,levels of IL-6,IL-18 in serum and liver tissue,and expression of miR-181b-5p in liver tissue were increased obviously(P<0.05).Compared with NAFLD model group,patho-logical damage of liver tissue in LncRNA MEG3 overexpression group was reduced,expressions of LncRNA MEG3,FOXP1 mRNA and protein in liver tissue were increased(P<0.05),levels of TG,TC,FFA,ALT and AST,liver coefficient,levels of IL-6,IL-18 in serum and liver tissue,and expression of miR-181b-5p in liver tissue were decreased(P<0.05);there was no obvious changes in each index of mice in negative control group(P>0.05).Compared with LncRNA MEG3 overexpression group,pathological damage of liver tissue in LncRNA MEG3 overexpression+miR-181b-5p mimics group was aggravated,expression of FOXP1 mRNA and protein in liver tissue was decreased(P<0.05),levels of TG,TC,FFA,ALT and AST,liver coefficient,levels of IL-6,IL-18 in serum and liver tissue,and expression of miR-181b-5p in liver tissue were increased(P<0.05).LncRNA MEG3 could target and down-regulate miR-181b-5p expression in liver parenchymal cells,and miR-181b-5p could target and down-regulate FOXP1 expression.Conclusion:Overexpression of LncRNA MEG3 can enhance the expression of FOXP1 by down-regulation of miR-181b-5p,thereby improving lipid metabolism,reducing inflammation and liver tissue damage,and ultimately repairing liver function in NAFLD mice.关键词
LncRNA MEG3/miR-181b-5p/FOXP1/非酒精性脂肪性肝病/作用机制Key words
LncRNA MEG3/miR-181b-5p/FOXP1/Non-alcoholic fatty liver disease/Action mechanism分类
医药卫生引用本文复制引用
方金鸣..LncRNA MEG3调节miR-181b-5p/FOXP1轴对非酒精性脂肪性肝病小鼠的作用机制研究[J].中国免疫学杂志,2025,41(4):885-892,8.基金项目
武汉市卫生健康委员会科研项目(WX19Y10). （WX19Y10）
