miR-27a-3p调控YAP1/TAZ通路对急性心肌梗死大鼠心功能的影响OA
Impact of miR-27a-3p on cardiac function in rats with acute myocardial infarction by regulating YAP1/TAZ pathway
目的:探讨miR-27a-3p调控Yes相关蛋白1(YAP1)/含PDZ结合基序(TAZ)通路对急性心肌梗死(AMI)大鼠心功能的影响.方法:双荧光素酶报告基因实验检测miR-27a-3p与YAP1的互作;构建AMI大鼠,造模成功的大鼠随机分为AMI组、NC agomir组(尾静脉注射NC agomir)、miR-27a-3p agomir组(尾静脉注射miR-27a-3p agomir)、PY-60组(尾静脉注射miR-27a-3p agomir+7 μmol/L YAP1激活剂PY-60),每组10只.另选10只大鼠为Sham组,Sham组和AMI组分别注射等量生理盐水.超声心动图检测大鼠心功能;ELISA试剂盒检测大鼠血清心肌损伤和炎症指标表达;qRT-PCR检测心肌组织miR-27a-3p、YAP1、TAZ mRNA表达;HE染色检测心肌组织病理学变化;TUNEL染色检测心肌细胞凋亡;Western blot检测心肌组织YAP1、TAZ蛋白表达.结果:Sham组心肌组织结构完整;AMI组和NC agomir组心肌结构破坏严重,表现为肌束断裂、细胞肥大及间隙水肿,伴有核固缩及显著炎症浸润;miR-27a-3p agomir组心肌细胞损伤减轻,炎症细胞浸润减少;PY-60组心肌细胞损伤加重,炎症细胞浸润加深.miR-27a-3p可靶向负调控YAP1.AMI组LVESD、LVEDD、YAP1、TAZ mRNA和蛋白表达、LDH、AST、CK-MB、α-HBDH、IL-1β、TNF-α水平、凋亡率高于Sham组,LVEF、LVFS、miR-27a-3p水平低于Sham组(P<0.05);miR-27a-3p agomir组LVESD、LVEDD、YAP1、TAZ mRNA和蛋白表达、LDH、AST、CK-MB、α-HBDH、IL-1β、TNF-α水平、凋亡率低于AMI组、NC agomir组,LVEF、LVFS、miR-27a-3p高于AMI组、NC agomir组(P<0.05);PY-60组LVESD、LVEDD、YAP1、TAZ mRNA和蛋白表达、LDH、AST、CK-MB、α-HBDH、IL-1β、TNF-α水平、凋亡率高于miR-27a-3p agomir组,LVEF、LVFS低于miR-27a-3p agomir组(P<0.05).结论:miR-27a-3p可能通过调控YAP1/TAZ通路改善AMI大鼠心功能.
Objective:To investigate impact of miR-27a-3p on cardiac function in rats with acute myocardial infarction(AMI)by regulating Yes-associated protein 1(YAP1)/transcriptional co-activator with PDZ-binding motif(TAZ)pathway.Methods:Dual luciferase reporter gene assay was used to detect interaction between miR-27a-3p and YAP1.AMI rats were constructed,and success-fully modeled rats were randomly grouped into AMI group,NC agomir group(tail vein injection of NC agomir),miR-27a-3p agomir group(tail vein injection of miR-27a-3p agomir),PY-60 group(tail vein injection of miR-27a-3p agomir+7 μmol/L YAP1 activator PY-60),with 10 rats in each group.Another 10 rats were designated as Sham group,and equal amounts of physiological saline were injected into both Sham group and AMI group.Echocardiography was used to detect cardiac function in rats.ELISA kits were used to detect myocardial damage and inflammatory indicators in rat serum.qRT-PCR was used to detect miR-27a-3p,YAP1 and TAZ mRNA expressions in myocardial tissue.HE staining was used to measure pathological changes of myocardial tissue.TUNEL staining was used to measure myocardial cell apoptosis.Western blot was used to detect YAP1 and TAZ proteins expressions in myocardial tissue.Results:Sham group had intact myocardial tissue structure.AMI and NC agomir groups exhibited marked myocardial disruption,in-cluding myofiber rupture,cellular hypertrophy,interstitial edema,nuclear condensation,and intense inflammation.miR-27a-3p agomir group showed reduced myocardial cell damage and decreased infiltration of inflammatory cells.Myocardial cell damage wors-ened and infiltration of inflammatory cells deepened in PY-60 group.miR-27a-3p could target and negatively regulate YAP1.AMI group had higher LVESD,LVEDD,YAP1,TAZ mRNA and protein expressions,LDH,AST,CK-MB,α-HBDH,IL-1β,TNF-α levels,and apoptosis rate than Sham group,and lower LVEF,LVFS and miR-27a-3p levels than Sham group(P<0.05).miR-27a-3p agomir group had lower LVESD,LVEDD,YAP1,TAZ mRNA and protein expressions,LDH,AST,CK-MB,α-HBDH,IL-1β,TNF-α levels,and apoptosis rate than AMI group and NC agomir group,and higher LVEF,LVFS levels and miR-27a-3p levels than AMI group and NC agomir group(P<0.05).PY-60 group had higher LVESD,LVEDD,YAP1,TAZ mRNA and protein expressions,LDH,AST,CK-MB,α-HBDH,IL-1β,TNF-α levels and apoptosis rate than miR-27a-3p agomir group,and lower LVEF,LVFS and miR-27a-3p levels than miR-27a-3p agomir group(P<0.05).Conclusion:miR-27a-3p may improve cardiac function in AMI rats by regulating YAP1/TAZ pathway.
公方娜;贾宏亮;单鸿伟
内蒙古医科大学附属医院急诊内科,呼和浩特 010000内蒙古医科大学附属医院急诊内科,呼和浩特 010000内蒙古医科大学附属医院急诊内科,呼和浩特 010000
医药卫生
miR-27a-3pYes相关蛋白1含PDZ结合基序急性心肌梗死心功能
miR-27a-3pYes-associated protein 1Transcriptional co-activator with PDZ-binding motifAcute myocardial infarctionCardiac function
《中国免疫学杂志》 2026 (8)
1828-1833,6
2022年度内蒙古自治区卫生健康科技计划项目(202201243)2022年度内蒙古医科大学联合项目计划(YKD2022LH025).
评论