[1]王咪,张鹏珂,张鹏,等.沉默调节蛋白6通过抑制心肌梗死后心肌细胞凋亡改善心脏功能障碍的机制研究[J].陕西医学杂志,2026,(4):435-439/445.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.001]
　WANG Mi,ZHANG Pengke,ZHANG Peng,et al.SIRT6 improves cardiac dysfunction by inhibiting cardiomyocyte apoptosis after myocardial Infarction[J].,2026,(4):435-439/445.[doi:DOI:10.3969/j.issn.1000-7377.2026.04.001]
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沉默调节蛋白6通过抑制心肌梗死后心肌细胞凋亡改善心脏功能障碍的机制研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年4期
页码:
435-439/445
栏目:
基础研究
出版日期:
2026-04-05

文章信息/Info

Title:
SIRT6 improves cardiac dysfunction by inhibiting cardiomyocyte apoptosis after myocardial Infarction
作者:
王咪; 张鹏珂; 张鹏; 于晓蕾; 赵晓洁; 王婷婷
（空军军医大学第二附属医院心血管内科，陕西 西安 710068）
Author(s):
WANG Mi; ZHANG Pengke; ZHANG Peng; YU Xiaolei; ZHAO Xiaojie; WANG Tingting
（Department of Cardiology,The Second Affiliated Hospital of Air Force Medical University,Xi’an 710068,China）
关键词:
缺血性心肌病; 急性心肌梗死; 凋亡; 沉默调节蛋白6; 心肌细胞; 心脏功能障碍
Keywords:
Ischemic cardiomyopathy; Acute myocardial infarction; Apoptosis; SIRT6; Cardiomyocytes; Cardiac dysfunction
分类号:
R 542.2
DOI:
DOI:10.3969/j.issn.1000-7377.2026.04.001
文献标志码:
A
摘要:
目的：急性心肌梗死（AMI）是缺血性心脏病的主要临床表现，是发病和死亡的重要原因。然而，缺血性心脏病及其相关心脏功能障碍的发病机制关键调节因子仍然存在争议。该研究旨在探讨沉默调节蛋白6（SIRT6）在AMI中的参与及其相关机制。方法：结扎左冠状动脉（LCA）诱导AMI小鼠模型。通过马松染色检测心肌梗死面积及纤维化程度，通过超声心动图评估心脏功能。用无糖和无血清培养基模拟心肌细胞营养剥夺。此外，将心肌细胞置于缺氧室（1%O2、5%CO2和94%N2）中进一步培养9 h用于体外诱导AMI模型。将Ad-SIRT6以及相应的阴性对照转染至心肌细胞中，观察SIRT6的作用。采用蛋白质印迹评估凋亡相关蛋白B细胞淋巴瘤2基因（Bcl-2）和Bcl-2相关X蛋白（Bax）的表达水平。结果：Masson染色结果显示，心肌梗死后，小鼠心肌梗死的面积增大，且纤维化程度加重，在一定程度上使心脏发生了重构，过表达SIRT6后能够减小心肌梗死面积，减轻心肌梗死小鼠的纤维化程度，减轻心脏重构；心脏超声结果表明，心梗后小鼠的心脏功能进行性下降，而SIRT6能够改善小鼠因心肌梗死导致的心脏功能下降。细胞实验结果表明，AMI组心肌细胞凋亡水平被激活。缺氧处理的心肌细胞中凋亡相关蛋白Bax的表达水平上调，而抗凋亡蛋白Bcl-2的表达水平下调；SIRT6的干预减少了心肌细胞凋亡相关蛋白Bax的表达，上调了抗凋亡蛋白Bcl-2的表达水平，减少了心肌细胞的凋亡。结论：SIRT6介导的凋亡信号通路在AMI损伤的发病机制中发挥重要作用，可能成为改善心梗后心脏功能的潜在治疗靶点。
Abstract:
Objective:Acute myocardial infarction （AMI） is considered as the primary clinical manifestation of ischemic heart disease and the leading cause of morbidity and mortality.However,the key regulatory factors underlying the pathogenesis of ischemic heart disease and its related cardiac dysfunction remain controversial.This study aims to explore the involvement of SIRT6 in AMI and its related mechanisms.Methods：Ligation of left coronary artery （LCA） was used to induce acute myocardial infarction model.Masson staining was used to evaluate the myocardial infarction area and fibrosis area.Echocardiography was used to evaluate cardiac function.The medium was replaced with a sugarfree and serumfree medium to simulate nutrient deprivation of cardiomyocytes.In aD-Dition,cardiomyocytes were further cultured for 9 hours in a hypoxia chamber （1%O2,5%CO2 and 94%N2） to simulate acute myocardial infarction model in vitro.Ad SIRT6 and the corresponding negative control were transfected into cardiomyocytes to observe the role of SIRT6.Western blotting was used to evaluate the expression levels of apoptosisrelated proteins Bcl-2 and Bax.Results:Masson staining showed that in myocardial infarction mice,the increased myocardial infarction area and aggravated degree of fibrosis were detected,which to some extent led to cardiac remodeling.Overexpression of SIRT6 could reduce the area of myocardial infarction,alleviate the degree of fibrosis in mice with myocardial infarction,and alleviate cardiac remodeling.The result of echocardiography showed that the cardiac function of myocardial infarction mice was decreased progressively,while SIRT6 could improve the decreased cardiac function caused by myocardial infarction in mice.Moreover,Western blotting showed that the apoptosis of cardiomyocytes in the AMI group was activated.The level of the apoptosisrelated protein Bax expression was upregulated in hypoxic cardiomyocytes,while the level of the antiapoptotic protein Bcl-2 expression was downregulated.The intervention of SIRT6 reduced the expression of the apoptosisrelated protein Bax in cardiomyocytes,upregulated the level of the antiapoptotic protein Bcl-2 expression,that reduced the apoptosis of cardiomyocytes.Conclusion:The apoptosis signal pathway mediated by SIRT6 plays an important role in the pathogenesis of AMI and may become a potential therapeutic target for improving cardiac function after myocardial infarction.

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备注/Memo

备注/Memo:
国家自然科学基金资助青年项目（82200404）；陕西省自然科学基础研究计划一般项目（2024JCYBQN0985，401291645001）
更新日期/Last Update: 2026-04-05