烟酰胺单核苷酸通过增强线粒体自噬抑制急性心肌梗死中的铁死亡  

Nicotinamide Mononucleotide Inhibits Ferroptosis in Acute Myocardial Infarction by Enhancing Mitophagy

作　　者：李雅佳 刘弟世闻 赵欣 韩雪钰 王学文 曹真 付韫韬 赵庆彦[1] LI Yajia;LIU Dishiwen;ZHAO Xin;HAN Xueyu;WANG Xuewen;CAO Zhen;FU Yuntao;ZHAO Qingyan(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Research Institute of Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院心血管内科武汉大学心血管病研究所心血管病湖北省重点实验室,湖北武汉430060

出　　处：《心血管病学进展》2025年第4期378-384,共7页Advances in Cardiovascular Diseases

基　　金：国家自然科学基金(82170312)。

摘　　要：目的探究烟酰胺单核苷酸(NMN)是否可通过调节线粒体自噬抑制铁死亡,改善急性心肌梗死(AMI)后的炎症反应和心脏功能。方法研究为前瞻性对照研究,30只成年雄性SD大鼠随机分为3组:对照组(Sham组)、AMI组和AMI+NMN组,每组10只。超声心动图检测各组SD大鼠左室舒张末容积、左室收缩末容积、左心室短轴缩短率和左室射血分数(LVEF)等指标;HE染色评估左心室的炎症反应水平;Masson染色检测左心室纤维化程度;普鲁士蓝染色检测组织的铁离子沉积;透射电镜检测组织的线粒体结构;蛋白质印迹法检测铁死亡相关指标线粒体铁蛋白(FTMT)、谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11),线粒体自噬相关指标PTEN诱导激酶1(PINK1)、微管相关蛋白1轻链3(LC3)-Ⅰ、LC3-Ⅱ和沉默信息调节因子1(SIRT1)的表达水平。结果与Sham组相比,AMI组大鼠左室舒张末容积和左室收缩末容积显著增加(P<0.05),左心室短轴缩短率和LVEF显著下降(P<0.05);左心室组织的炎症水平、纤维化程度和铁离子沉积增加,线粒体损伤程度加重;FTMT、GPX4、SLC7A11和SIRT1蛋白的表达水平明显下降(P<0.05),PINK1蛋白表达水平和LC3-Ⅱ与LC3-Ⅰ蛋白表达水平的比值上升(P<0.05)。与AMI组相比,AMI+NMN组的LVEF增加(P<0.05);左心室组织的炎症水平、纤维化程度和铁离子沉积降低,线粒体损伤程度减轻;FTMT、GPX4、SLC7A11和SIRT1蛋白的表达水平升高(P<0.05),PINK1蛋白表达水平和LC3-Ⅱ与LC3-Ⅰ蛋白表达水平的比值上升(P<0.05)。结论大鼠AMI后,心肌组织内线粒体自噬水平升高,但不能适应缺氧极端环境的变化,心肌细胞铁死亡增加,补充NMN可上调SIRT1的表达,增强线粒体自噬功能,及时清除损伤的线粒体,减轻心肌细胞铁死亡,从而改善大鼠AMI后的炎症反应和心脏功能。Objective To investigate whether nicotinamide mononucleotide(NMN)can inhibit ferroptosis in cardiomyocytes and improve inflammatory response and cardiac function after acute myocardial infarction(AMI)by modulating mitophagy.Methods In this prospective controlled study,30 adult male SD rats were randomized into 3 groups:the Sham group,the AMI group,and the AMI+NMN group,with 10 rats in each group.Echocardiography was used to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular fraction shortening(LVFS),and left ventricular ejection fraction(LVEF)in the left ventricle of SD rats in each group;HE staining was used to assess the level of the inflammatory response of the left ventricle;Masson staining was used to detect the degree of fibrosis of the left ventricle;Prussian blue staining was used to detect tissue iron ion deposition;transmission electron microscopy to detect the mitochondrial structure of tissues;Western blotting to detect the expression levels of ferroptosis-related indexes mitochondrial ferritin(FTMT),glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11)as well as mitochondrial autophagy-related indexes PTEN-induced kinase 1(PINK1),microtubule-associated protein 1 light chain 3(LC3)-Ⅰand LC3-Ⅱ,and silence information regulator 1(SIRT1).Results Compared with the Sham group,the LVEDV and LVESV in the AMI group were significantly higher(P<0.05),and the LVFS and LVEF were significantly lower(P<0.05);the level of inflammation,the degree of fibrosis,and the iron deposition in the left ventricular tissue were increased,and the degree of mitochondrial damage was aggravated;the expression levels of FTMT,GPX4,SLC7A11,and SIRT1 were significantly lower(P<0.05),and the PINK1 protein expression level and the ratio of the LC3-Ⅱto LC3-Ⅰ protein expression level increased (P<0. 05). Compared with the AMI group,the LVEF of the AMI+NMN group was increased (P<0. 05);the inflammation level,degree of fibrosis,and iron deposition o

关 键 词：急性心肌梗死 烟酰胺单核苷酸 烟酰胺腺嘌呤二核苷酸 线粒体自噬 铁死亡 

分 类 号：R542.2[医药卫生—心血管疾病]