摘要
目的通过心脏磁共振特征追踪技术分析实验性自身免疫性心肌炎(EAM)模型三维应变特征,探索铁死亡在心肌损伤中的作用及其与应变参数的相关性。材料与方法皮下注射等体积猪心肌肌球蛋白与完全弗氏佐剂乳化的混合物,诱导Lewis大鼠发生EAM。EAM组15只和对照组15只大鼠均接受7T心脏磁共振检查,21 d后处死。心脏磁共振评估指标包括左心室功能和心肌应变。通过组织病理学、血清学、Western blot和PCR检测心肌损伤和铁死亡标志物。结果猪心肌肌球蛋白免疫21 d后,EAM组大鼠左心室射血分数显著降低(t=7.86,P<0.001)。与对照组相比,EAM组整体、基底段、中间段及心尖段径向应变、周向应变、纵向应变的绝对值均显著下降(t=2.61~10.45,P<0.05)。EAM组血清乳酸脱氢酶、心肌肌钙蛋白I及干扰素γ水平显著高于对照组(t=16.54、21.20、16.06,P<0.001),提示心肌损伤。普鲁士蓝染色证实EAM组心肌组织存在铁沉积。EAM组丙二醛、活性氧水平较对照组显著升高(t=15.75、3.47,P<0.01),超氧化物歧化酶活性降低(t=14.21,P<0.001)。Western blot和组织病理学结果显示EAM组铁蛋白重链蛋白表达上调(t=5.15,P<0.01)。EAM大鼠溶质载体家族7成员11/谷胱甘肽/谷胱甘肽过氧化物酶4轴在血清、mRNA及蛋白水平均显著降低(t=7.73~30.14,P<0.001)。相关性分析显示,整体周向应变及纵向应变与铁死亡标志物呈显著相关(r=-0.854~0.829,P<0.05)。结论心脏磁共振特征追踪技术可通过心肌应变定量评价EAM心肌损伤,心肌损伤与铁死亡的参与有关,铁死亡标志物与心肌应变相关。
Purpose To quantitatively evaluate myocardial three-dimensional strains using cardiac magnetic resonance feature tracking,investigate whether ferroptosis contributes to myocardial injury in experimental autoimmune myocarditis(EAM),and explore the relationship between strains and ferroptosis biomarkers.Materials and Methods EAM was induced in Lewis rats via subcutaneous injections with porcine cardiac myosin emulsified in same amount of complete Freund’s adjuvant.Both EAM(n=15)and control(n=15)rats underwent 7T cardiac magnetic resonance and were euthanatized at day 21.Cardiac magnetic resonance assessments included left ventricular function and strains.The cardiac damage and ferroptosis-related markers were measured with histopathology,serology,Western blot and polymerase chain reaction.Results The left ventricular ejection fraction declined in the rats post-immunization with porcine cardiac myosin at day 21(t=7.86,P<0.001).Global,basal,middle and apical strains encompassing radial strain,circumferential strain and longitudinal strain were significantly lower in the EAM group compared to the control group(t=2.61-10.45,P<0.05).Cardiac and inflammatory biomarkers,including lactate dehydrogenase,cardiac troponin I and interferonγindicated myocardial injury in EAM group compared to the control group(t=16.54,21.20,16.06,all P<0.001).Prussian blue staining revealed iron overload in EAM group.Compared to the control group,malondialdehyde and reactive oxygen significantly increased in EAM group(t=15.75,3.47,both P<0.01),and superoxide dismutase were significantly decreased(t=14.21,P<0.001).Western blot and histopathology showed that the protein expression of ferritin heavy chain was significantly higher in the EAM group compared to the control group(t=5.15,P<0.01).The solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 axis was down regulated at serum,mRNA and protein expression levels in EAM group(t=7.73-30.14,all P<0.001).Global circumferential and longitudinal strains were significantly associated with ferroptosis biomarkers(r=-0.854-0.829,all P<0.05).Conclusion Cardiac magnetic resonance feature tracking has the potential to quantitatively evaluate myocardial damage of EAM which involves ferroptosis.The strains are related with ferroptosis biomarkers.
作者
王春华
王哲涛
朱静
张钰
周鹏
郜发宝
WANG Chunhua;WANG Zhetao;ZHU Jing;ZHANG Yu;ZHOU Peng;GAO Fabao(Department of Radiology,West China Hospital,Sichuan University,Chengdu 610041,China;不详)
出处
《中国医学影像学杂志》
北大核心
2025年第5期485-492,共8页
Chinese Journal of Medical Imaging
基金
四川省干部保健科研项目(川干研2024-804)
西藏自治区科学技术厅重点研发计划(XZ202402ZY0003)
四川省干部保健科研项目(川干研2024-115)
四川省自然科学基金项目(2023NSFSC1717)
北京医学奖励基金会项目(YXJL-2024-0350-0179)。
关键词
心肌炎
免疫系统疾病
磁共振成像
特征追踪
心肌应变
铁死亡
大鼠
Myocarditis
Immune system diseases
Magnetic resonance imaging
Feature tracking
Strain
Ferroptosis
Rats
作者简介
通信作者:郜发宝.fabaogao@outlook.com。
