环状RNA ACAP2调节微小RNA-421与B细胞易位基因2轴对心肌梗死大鼠心肌损伤的影响  

Effect of circACAP2 on myocardial injury in rats with myocardial infarction by regulating miR-421/BTG2 axis

作　　者：黎姗姗[1] 许文 杨熙 涂琳[1] 周海燕 Li Shanshan;Xu Wen;Yang Xi;Tu Lin;Zhou Haiyan(Department of Cardiovascular Medicine,Guiyang First People's Hospital,Guiyang 550000,Guizhou Province,China)

机构地区：[1]贵阳市第一人民医院心血管内科,550000 [2]贵州医科大学附属医院心内科

出　　处：《中华老年心脑血管病杂志》2024年第6期688-693,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：2022年贵州省科技计划重点项目[黔科合基础-ZK(2022)重点043]。

摘　　要：目的探讨环状RNA ACAP2(circACAP2)调节微小RNA(miR)-421/B细胞易位基因2(BTG2)轴对心肌梗死(MI)大鼠心肌损伤的影响。方法构建MI大鼠模型和H9c2细胞模型,将80只大鼠分为假手术组、MI组、小干扰RNA-阴性对照(si-NC)组、si-circACAP2组、pcDNA3.1组、pcDNA3.1-circACAP2组、pcDNA3.1-circACAP2+模拟物(mimic)NC组、pcDNA3.1-circACAP2+miR-421 mimic组,每组各10只。将缺氧H9c2细胞置于24孔板中,瞬时转染细胞,分为缺氧组、缺氧+si-NC组、缺氧+si-circACAP2组、缺氧+pcDNA3.1组、缺氧+pcDNA3.1-circACAP2组、缺氧+pcDNA3.1-circACAP2+mimic NC组、缺氧+pcDNA3.1-circACAP2+miR-421 mimic组,另取正常培养的H9c2细胞作为对照组。检测大鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、心肌梗死情况、心肌组织病理变化、circACAP2、miR-421、BTG2 mRNA表达情况、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性、H9c2细胞活力和凋亡、心肌组织BTG2蛋白表达、H9c2细胞BTG2蛋白表达。结果MI组circACAP2、BTG2 mRNA表达高于假手术组(1.84±0.21 vs 1.00±0.10,1.68±0.17 vs 1.00±0.10),miR-421表达低于假手术组(0.49±0.05 vs 1.00±0.11,P<0.05);与假手术组比较,MI组梗死面积、CK-MB、LDH活性升高,LVFS、LVEF降低(P<0.05)。与si-NC组比较,si-circACAP2组心肌损伤减轻,LVFS、LVEF升高,梗死面积、CK-MB、LDH活性降低(P<0.05);与缺氧+si-NC组比较,缺氧+si-circACAP2组细胞活力升高,凋亡率、CK-MB和LDH活性降低(P<0.05)。与pcDNA3.1组比较,pcDNA3.1-circACAP2组心肌损伤加重,LVFS、LVEF降低,梗死面积、CK-MB、LDH活性升高(P<0.05);与缺氧+pcDNA3.1组比较,缺氧+pcDNA3.1-circACAP2组细胞活力降低,凋亡率、CK-MB、LDH活性升高(P<0.05)。结论circACAP2在MI大鼠和H9c2细胞中表达上调,沉默circACAP2可能通过调节miR-421/BTG2轴改善心脏功能,减少心肌损伤,提高心肌细胞活力。Objective To investigate the effect of circular RNA(circRNA)ACAP2 on myocardial injury in MI rats by regulating the miR-421/B cell translocation gene 2(BTG2)axis.Methods A rat MI model and an H9c2 myocardial cell model were constructed.A total of 80 rats were divided into sham operation group,MI group,small interfering RNA-negative control(si-NC)group,si-circACAP2 group,overexpression control(pcDNA3.1)group,pCDNA3.1-circACAP2 group,pCDNA3.1-circACAP2+mimic NC group,and pCDNA3.1-circACAP2+miR-421 mimic group,with 10 rats in each group.H9c2 cells were divided into hypoxia group,hypoxia+si-NC group,hypoxia+si-circACAP2 group,hypoxia+pcDNA3.1 group,hypoxia+pcDNA3.1 circACAP2 group,hypoxia+pcDNA3.1 circACAP2+mimic NC group,hypoxia+pcDNA3.1 circACAP2+miR-421 mimic group,and control group.LVEF,LVFS,myocardial infarction,pathological changes of myocardial tissue,and circACAP2,miR-421 and BTG2 mRNA expression,LDH,CK-MB activity,H9c2 cardiomyocyte viability and apoptosis,BTG2 protein expression in myocardial tissue,and BTG2 protein expression in H9c2 cardiomyocytes were detected in each group.Results Compared with the sham operation group,higher mRNA levels of circACAP2(1.84±0.21 vs 1.00±0.10)and BTG2(1.68±0.17 vs 1.00±0.10),larger infarct size,stronger activities of CK-MB and LDH,while decreased expression of miR-421(0.49±0.05 vs 1.00±0.11)and LVFS and LVEF values were observed in the MI group(P<0.05).Compared with the si-NC group,the si-circACAP2 group had alleviated myocardial injury,increased LVFS and LVEF values,and decreased infarct size and CK-MB and LDH activities(P<0.05).Significantly increased cell viability,and reduced apoptotic rate and CK-MB and LDH activities were observed in the hypoxia+si-circACAP2 group than the hypoxia+si-NC group(P<0.05).Compared with the pcDNA3.1 group,myocardial injury was aggravated,LVFS and LVEF were decreased,and infarct size and CK-MB and LDH activities were increased in the pcDNA3.1-circACAP2 group(P<0.05);Compared with the hypoxia+pcDNA3.1 group,the hypoxia+PCDNA3.1-circACA

关 键 词：肌细胞 心脏 心肌损伤 微小RNA-421/B细胞易位基因2轴 环状RNA ACAP2 心肌梗死大鼠 

分 类 号：R542.22[医药卫生—心血管疾病]