GLP-1RAs通过调控LINC01180/miR-30b/CPT1A通路改善脂毒性氧化应激  

GLP-1RAs Ameliorates Lipotoxic Oxidative Stress by Regulating the LINC01180/miR-30b/CPT1A Pathway

作　　者：张志莹 闫爽[1] ZHANG Zhiying;YAN Shuang(Department of Endocrinology,The Fourth Affiliated Hospital of Harbin Medical University,Heilongjiang 150001,China)

机构地区：[1]哈尔滨医科大学附属第四医院内分泌科,150001

出　　处：《医学研究杂志》2023年第12期76-82,共7页Journal of Medical Research

基　　金：黑龙江省省属高等学校基本科研业务费科研项目(2020-KYYWF-14);黑龙江省卫生健康委员会科研课题(2020-095)。

摘　　要：目的探讨胰高血糖素样肽-1受体激动剂(glucagon-like peptide-1 receptor agonists,GLP-1RAs)改善胰岛细胞脂毒性氧化应激,分析其机制是否与调控LINC01180/miR-30b/CPT1A通路表达有关。方法通过基因芯片和生物信息学分析方法预测LINC01180可能调控microRNA及相关蛋白。在体内和体外建模,分为对照组、高脂组、GLP-1RAs组。检测丙二醛(malondialdehyde,MDA)含量和总抗氧化能力(total antioxidant capacity,T-AOC)活性。苏木精-伊红染色及免疫组化Reg3r分析。实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测LINC01180、miR-30b和CPT1A表达量。Western blot法检测CPT1A的蛋白表达水平。通过瞬时转染技术分别抑制和过表达LINC01180,RT-qPCR检测转染后miR-30b和CPT1A表达水平。结果生物信息学分析结果表明,LINC01180/miR-30b/CPT1A形成ceRNA调控网络。GLP-1RAs模型中脂毒性氧化应激明显改善,LINC01180表达量下降,miR-30b和CPT1A表达量上升。转染LINC01180表达显著影响miR-30b和CPT1A的表达量。结论GLP-1RAs通过下调LINC01180的表达,上调miR-30b和CPT1A表达,改善脂毒性氧化应激。Objective To investigate the effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on lipotoxic oxidative stress in islet cells,and to explore whether the mechanism is related to the regulation of LINC01180/miR-30b/CPT1A pathway.Methods Gene chips and bioinformatics analysis predicted that LINC01180might regulate microRNA and related proteins.In vivo and in vitro modeling,the models were divided into control group,high-fat group and GLP-1RAs group.The content of malondialdehyde(MDA)and the activity of total antioxidant capacity(T-AOC)were detected.Hematoxylin-eosin staining and immunohistochemical Reg3γanalysis were determined either.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression levels of LINC01180,miR-30b and CPT1A.The protein expression levels of CPT1A was detected by Western blot.LINC01180 was inhibited and overexpressed by transient transfection,the expression levels of miR-30b and CPT1A after transfection were detected by RT-qPCR.Results Bioinformatics analysis showed that LINC01180/miR-30b/CPT1A formed ceRNA regulatory network.The lipotoxic oxidative stress was significantly improved in GLP-1RAs model,and the expression levels of LINC01180 was decreased,while the expression levels of miR-30b and CPT1A were increased.Transfection of LINC01180significantly affected the expression levels of miR-30b and CPT1A.Conclusion GLP-1RAs ameliorates lipotoxic oxidative stress by down-regulating the expression levels of LINC01180 and up-regulating the expression of miR-30b and CPT1A.

关 键 词：胰高血糖素样肽-1受体激动剂 LINC01180 miR-30b 肉碱棕榈酰基转移酶1A 脂毒性氧化应激 

分 类 号：R58[医药卫生—内分泌]