中国比较医学杂志2025,Vol.35Issue(12):52-64,13.DOI:10.3969/j.issn.1671-7856.2025.12.005
miR-574-5p通过靶向TNS1改善心脏骤停后小鼠心功能
miR-574-5p improves cardiac function in mice after cardiac arrest by targeting the tensin 1 gene
摘要
Abstract
Objective To examine the regulatory relationship between the tensin 1(TNS1)gene and miR-574-5p in cardiac arrest,assess its clinical significance,and verify the therapeutic potential of targeted inhibition of miR-574-5p.Methods Oxygen-glucose deprivation/reoxygenation(OGD/R)cardiomyocyte and mouse asphyxia cardiac arrest/cardiopulmonary resuscitation(ACA/CPR)models were established.Expression levels of miR-574-5p and TNS1 were detected by RT-qPCR.Protein expression levels of TNS1 in cardiomyocytes were detected by Western blot.The targeting relationship between miR-574-5p and TNS1 was verified by dual-luciferase reporter gene assay.Cell viability was detected by Cell Counting Kit-8 assay,and apoptosis was measured by flow cytometry.Serum levels of the cardiac injury marker cardiac troponin I(cTnI)and the oxidative stress markers malondialdehyde and 4-hydroxynonenal were detected by enzyme-linked immunosorbent assay.The cardiac function indices dp/dtmin and dp/dtmax were evaluated using a hemodynamic monitoring system,and cardiac function parameters,including left ventricular ejection fraction and left ventricular fractional shortening,were determined by echocardiography.Results OGD/R treatment significantly upregulated the expression of miR-574-5p and inhibited the mRNA and protein expression of TNS1 in cardiomyocytes,while inhibition of miR-574-5p improved cardiomyocyte survival and alleviated oxidative stress injury(P<0.05).In the ACA/CPR model,cardiac function indices were significantly improved(P<0.05),cardiac injury and oxidative stress markers were reduced(P<0.05),and the upregulation of miR-574-5p and downregulation of TNS1 expression patterns in myocardial tissues were reversed in the miR-574-5p antagonist group(P<0.05).Conclusions This study confirmed that targeted inhibition of miR-574-5p can improve cardiac function by upregulating the expression of TNS1,providing a new therapeutic target for myocardial protection after cardiac arrest.关键词
心脏骤停/miR-574-5p/TNS1/心功能/氧化应激Key words
cardiac arrest/miR-574-5p/TNS1/cardiac function/oxidative stress分类
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王秋艳,王晓蕾,于美军,陈静,娄序笙..miR-574-5p通过靶向TNS1改善心脏骤停后小鼠心功能[J].中国比较医学杂志,2025,35(12):52-64,13.基金项目
秦皇岛市科技计划项目(202301A083). (202301A083)