2025 年第 5 期 第 20 卷

利用高分辨率磁共振成像技术探究射血分数保留型心力衰竭小鼠的大脑结构改变

Exploration of the changes of brain structure in mice with heart failure with preserved ejection fraction by high-resolution magnetic resonance imaging

作者：张新宇李国旗杨洁李依璘李玉琳

英文作者：Zhang Xinyu Li Guoqi Yang Jie Li Yilin Li Yulin

单位：首都医科大学附属北京安贞医院北京市心肺血管疾病研究所血管生物研究室，北京100029

英文单位：Vascular Biology Research Laboratory Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing Anzhen Hospital Capital Medical University Beijing 100029 China

关键词：射血分数保留型心力衰竭；大脑结构；磁共振成像

英文关键词：Heartfailurewithpreservedejectionfraction;Brainstructure;Magneticresonanceimaging

• 摘要：

• 目的 本研究旨在利用高分辨率磁共振成像（MRI）技术探究射血分数保留型心力衰竭（HFpEF）小鼠的大脑结构改变，以期为理解该病的病理生理机制和开发新的治疗方法提供科学依据。方法 选取无特定病原体级雄性C57BL/6J小鼠60只，采用随机数字表法按体重分层后分为对照组和HFpEF组，各30只。对照组正常饮食，自由饮用普通水。HFpEF组高脂饮食联合左旋硝基精氨酸甲酯双打击构建HFpEF模型。利用高分辨率MRI技术结合体素形态学分析技术，对小鼠大脑结构进行评估，并通过统计分析确定显著变化区域。结果 与对照组相比，HFpEF组小鼠干预36、60周时右海马旁回区域灰质体积显著增加［（0.92±0.08）、（1.05±0.09）mm3比（0.78±0.06）mm3］（均P＜0.05），峰值MNI坐标为X=-11.4,Y=-14.1,Z=16.2，F值为47.62，团块大小为2 060个体素。弓状核和室旁核在36周和60周HFpEF组中的灰质体积显著大于对照组，腹内侧核和背外侧核在60周HFpEF组中的灰质体积也表现出显著增加（P＜0.05或P＜0.01）。此外，前视丘脑区在60周HFpEF组中的灰质体积同样显著大于对照组（P＜0.01）。结论 HFpEF可导致小鼠大脑结构的显著改变，特别是海马旁回和下丘脑部分核团，这些结构变化可能与HFpEF的病理生理机制密切相关。

• Objective The purpose of this study is to explore the changes of brain structure in mice with heart failure with preserved ejection fraction (HFpEF) using high-resolution magnetic resonance imaging (MRI), in order to provide scientific basis for understanding the pathophysiological mechanism of the disease and developing new treatment methods. Methods Sixty specific pathogen free male C57BL/6J mice were selected and divided into control group and HFpEF group by body weight stratification, with 30 mice in each group. The control group was given normal diet and drinking ordinary water freely.In HFpEF group, HFpEF model was established by high-fat diet combined with L-nitroarginine methyl ester double hit. The brain structure of mice was assessed by high-resolution MRI combined with the voxel-based morphometry technique, and significant regions were identified by statistical analysis. Results Compared with the control group, the HFpEF group had a significant increase in gray matter volume in the right parahippocampal gyrus at 36 and 60 weeks of intervention［(0.92±0.08), (1.05±0.09)mm3 vs (0.78±0.06)mm3］(both P＜0.05). The peak MNI coordinates were X=-11.4, Y=-14.1, Z=16.2, F value was 47.62, and the cluster size was 2 060 voxels. The gray matter volume of arcuate nucleus and paraventricular nucleus of the HFPEF group in the 36 week and 60 week were significantly greater than those of the control group, and the gray matter volume of ventromedial nucleus and dorsolateral nucleus of the HFPEF group also showed a significant increase in the 60 week (P＜0.05 or P＜0.01). In addition, the gray matter volume of the anterior thalamus of the HFPEF group was also significantly greater in the 60 week than that of the control group(P＜0.01). Conclusion HFpEF can lead to significant changes in brain structure in mice, especially in the parahippocampal gyrus and some nuclei of the hypothalamus. These structural changes may be closely related to the pathophysiological mechanism of HFpEF.