有氧运动抑制心脏Hmox-1/GPX4介导的铁死亡缓解糖尿病小鼠心室重构  

Aerobic exercise inhibited cardiac Hmox-1/GPX4 mediating ferroptosis to alleviate cardiac remodeling in diabetic cardiomyopathy

作　　者：王婷 邹岩[3] 李海燕[4] 王永华[3] WANG Ting;ZOU Yan;LI Haiyan;WANG Yonghua(Department of Ultrasound,Shaoxing People’s Hospital,Shaoxing Hospital,Zhejiang University School of Medicine,Shaoxing 312000,China;Department of Cardiology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Department of Physical Education,Wenzhou Medical University,Wenzhou 325035,China;Department of Rehabilitation,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]绍兴市人民医院浙江大学绍兴医院超声科,浙江绍兴312000 [2]温州医科大学附属第一医院心内科,浙江温州325015 [3]温州医科大学体育部,浙江温州325035 [4]温州医科大学附属第一医院康复科,浙江温州325015

出　　处：《温州医科大学学报》2023年第5期370-378,共9页Journal of Wenzhou Medical University

基　　金：国家自然科学基金项目(81501954)。

摘　　要：目的:阐明有氧运动通过抑制心脏铁死亡延缓糖尿病诱导的心室重构。方法:雄性C57BL/6小鼠和db/db自发糖尿病小鼠或C57BL/6小鼠予高脂喂养(HFD)联合链脲佐菌素(STZ)构建糖尿病模型(HFD+STZ),根据是否有氧运动进行分组。小鼠心功能采用超声心动图检测,用伊红苏木素(HE)染色观测心肌形态,用马松或天狼星红染色检测纤维化,并提取心脏组织蛋白和mRNA检测铁死亡相关指标,免疫组化检测心脏4-羟基壬烯醛(4-HNE)表达。结果:与对照组小鼠相比,db/db小鼠或HFD+STZ小鼠心肌肥厚加重,胶原纤维沉积增多,收缩能力下降,心脏组织血红素加氧酶1(Hmox-1)表达、4-HNE水平显著增加,谷胱甘肽过氧化物酶4(GPX4)表达明显降低(P<0.05);经跑台运动训练后心脏改变得到逆转,且Hmox-1表达、4-HNE水平表达降低,GPX4表达增加(P<0.05)。结论:有氧运动可以通过抑制心脏铁死亡来改善糖尿病心肌病的心肌肥大及纤维化。Objective:To illuminate the protective effect of aerobic exercise inhibiting ferroptosis by heme oxygenase-1(Hmox-1)and glutathione peroxidase 4(GPX4)against diabetic myocardial remodeling.Methods:Male C57BL/6 mice(as control)and db/db mice were fed with ordinary diet,which were spontaneously induced with type 2 diabetes,and mice fed with high-fat diet(HFD)and streptozotocin(STZ)-induced type 2 diabetes mice were treated with 12 weeks treadmill training.Then,cardiac function was examined by echocardiography HE,Masson’s staining and Sirius staining were respectively used to measure cardiac fibrosis andmorphology.In addition,mRNA and protein of GPX4 and Hmox-1 levels were detected by real-time quantitative polymerase chain reaction or Western blot.And cardiac 4-HNE was detected by immunohistochemical method.Results:Compared with the controls,both the heart of db/db mice and HFD+STZ induced mice presented by increased cardiac Hmox-1 and 4-HNE expression,decreased cardiac GPX4 level,accompanied by a reduction of cardiac dysfunction and cardiac hypertrophy and fibrosis.However,these abnormal changes were reversed by aerobic exercise,reflected by improved cardiac function,downregulated Hmox-1 and 4-HNE level,markedly activated GPX4(P<0.05).Conclusion:Aerobic exercise inhibited cardiac ferroptosis to reverse cardiac remodeling in diabetic mice.

关 键 词：铁死亡 有氧运动 心肌纤维化 心肌肥大 糖尿病 小鼠 

分 类 号：R542.2[医药卫生—心血管疾病]