中国医科大学学报2024,Vol.53Issue(6):516-524,9.DOI:10.12007/j.issn.0258-4646.2024.06.006
circFAT1调节miR-211-5p/CCND2轴对糖尿病心肌病大鼠心肌损伤的影响
circFAT1 affects myocardial injury in rats with diabetic cardiomyopathy by regulating the miR-211-5p/CCND2 axis
摘要
Abstract
Objective To explore the effect of circFAT1 on myocardial injury in rats with diabetic cardiomyopathy(DCM)and the regu-latory mechanism of circFAT1 on the miR-211-5p/CCND2 axis.Methods A DCM rat model was established by injecting rats with high glucose and high fat feed combined with STZ.The rats were randomly separated into DCM,circ-NC,circFAT1,circFAT1+agomir-NC,and circFAT1+miR-211-5p agomir groups,with 20 rats in each group;rats fed regular feed were used as control.Real-time PCR was used to detect the levels of circFAT1,miR-211-5p,and CCND2in myocardial tissue and Western blotting was used to detect CCND2 expression in myocardial tissue.The levels of fasting blood glucose(FBG),total cholesterol(TC),and triglycerides(TG)of rats were recorded.Car-diac ultrasound was used to detect the cardiac function of rats.Furthermore,HE and Masson staining were used to observe the pathological morphology of myocardial tissue and TUNEL staining was used to detect myocardial apoptosis.Additionally,ELISA was used to detect the levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Double luciferase reporter gene assay was used to verify the targeting relationship among circFAT1,miR-211-5p,and CCND2.Results Compared with the control group,the expression of circFAT1 and CCND2mRNA and protein and the levels of LVEF and LVFS decreased in the DCM group(P<0.05)whereas,the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-αincreased(P<0.05).Compared with the DCM group,the levels of circFAT1,CCND2mRNA and protein,LVEF,and LVFS increased in the circFAT1 group(P<0.05),whereas the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-α decreased(P<0.05).Furthermore,miR-211-5p agomir reversed the protective effect of circFAT1 on DCM myocardial injury,and the expression of CCND2mRNA and protein decreased(P<0.05).Conclu-sion circFAT1 alleviates myocardial tissue damage in rats with DCM by regulating the miR-211-5p/CCND2 axis.关键词
circFAT1/miR-211-5p/细胞周期蛋白D2/糖尿病心肌病/心肌损伤Key words
circFAT1/miR-211-5p/cyclin D2/diabetic cardiomyopathy/myocardial damage分类
医药卫生引用本文复制引用
谷君,许峥嵘,史丽,任卫东,左丽娟,张秋子..circFAT1调节miR-211-5p/CCND2轴对糖尿病心肌病大鼠心肌损伤的影响[J].中国医科大学学报,2024,53(6):516-524,9.基金项目
河北省卫生厅医学科学研究课题计划项目(20190875) (20190875)
张家口市科技计划财政资助项目(1911021D-7) (1911021D-7)