miRNA-181a在非酒精性脂肪性肝病中的作用及其机制  

Role and mechanism of miRNA-181a in nonalcoholic fatty liver disease

作　　者：黄瑞贤[1] 段晓燕[1] 刘晓琳[1] 曹海霞[1] 汪余勤[1] 范建高[1] 汪保灿[1] Huang Ruixian;Duan Xiaoyan;Liu Xiaolin;Cao Haixia;Wang Yuqin;Fan Jiangao;Wang Baocan(Department of Gastroenterology,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院消化科,上海200092

出　　处：《中华肝脏病杂志》2021年第12期1177-1181,共5页Chinese Journal of Hepatology

摘　　要：目的探讨miRNA-181a(miR-181a)对非酒精性脂肪性肝病的影响及其可能的机制。方法使用棕榈酸处理HepG2细胞构建非酒精性脂肪性肝病细胞模型,检测细胞内miR-181a的表达及脂质沉积。用转化生长因子-β处理细胞检测其对miR-181a表达的影响。通过调控HepG2细胞miR-181a的表达水平,分别检测转染miR-181a模拟物和抑制物后HepG2细胞内miR-181a表达、脂质沉积和还原型谷胱甘肽和活性氧水平。通过实时荧光定量PCR和蛋白质印迹法对生物信息学预测的miR-181a靶基因进行验证。两组独立样本间比较采用独立样本t检验,多组间比较资料特征符合正态分布且方差齐性,采用单因素方差分析。结果棕榈酸处理后HepG2中脂质沉积明显增多,miR-181a表达水平显著高于对照组。HepG2细胞转染miR-181a抑制物后,miR-181a表达下调,甘油三酯和活性氧下降,还原型谷胱甘肽升高,预测靶基因沉默信息调节因子2相关酶1的mRNA和蛋白表达量上调;而转染miR-181a模拟物后,结果与上述改变相反。结论miR-181a参与非酒精性脂肪性肝病的脂质沉积并促进脂质过氧化,miR-181a可能是通过抑制沉默信息调节因子2相关酶1的表达来影响非酒精性脂肪性肝病的发病机制及进展。Objective To investigate the role and probable mechanism of miRNA-181a in nonalcoholic fatty liver disease.Methods HepG2 cells were treated with palmitic acid to construct a nonalcoholic fatty liver disease cell model,and the expression of miR-181a and lipidosis in the cells were measured.Transforming growth factor-β(TGF-β)was used to examine the effect of miR-181a expression in HepG2 cells.The miR-181a,lipidosis,reduced glutathione and reactive oxygen species(ROS)were determined by controlling and regulating the miR-183 expression levels after transfection with miR-181 mimics and inhibitors in HepG2 cells.The miR-181a target genes were predicted by bioinformatics analysis,and verified by real-time fluorescent quantitative PCR and western blotting.The independent sample t-test was used for the comparison between the two independent samples,and the comparison between multiple groups were accorded with the normal distribution,homogeneity of variance,and one-way analysis of variance.Results Lipidosis was significantly increased after palmitic acid treatment in HepG2 cells,and the expression level of miR-181a was significantly increased than control group.After HepG2 cells were transfected with miR-181a inhibitors,the expression of miR-181a,triglycerides and reactive oxygen species were down-regulated,and reduced glutathione,predicting the mRNA and protein expression of target gene silencing information regulator 2 related enzyme 1 were up-regulated.However,the results were contrary to the above changes after transfection with miR-181a mimics.Conclusion miR-181a participates in lipidosis and promotes lipid peroxidation in nonalcoholic fatty liver disease.miR-181a may affect the pathogenesis and progression of nonalcoholic fatty liver disease by inhibiting the expression of silencing information regulator 2 related enzyme 1.

关 键 词：非酒精性脂肪性肝病 转化生长因子 miR-181a SIRT1 

分 类 号：R575.5[医药卫生—消化系统]