压力超负荷心衰小鼠模型的心脏结构和功能 病理进程特征
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1.华南农业大学兽医学院,广州 510642; 2. 广东省实验动物监测所,广东省实验动物重点实验室,广州 510633

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Structural and functional pathological characteristics of pressure-overload induced heart failure mouse model
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1.College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. 2. Guangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory for Laboratory Animals, Guangzhou 510633

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    摘要:

    目的 建立小鼠心衰模型,应用超声影像学和病理学技术综合评价疾病发展过程中的特征性的心脏功能和结构的改变。 方法 应用主动脉弓缩窄(transverse aortic constriction,TAC)手术技术建立压力超负荷致小鼠心衰模型,造模前 0 周和造模后 2、4、8 周采集主动脉弓缩窄处血流多普勒估测血管承受压力,采集 B 型和 M 型超声图像评价心脏结构左室收缩功能,采集二尖瓣口血流多普勒结合二尖瓣环组织多普勒评价心脏舒张功能,采 集心脏组织进行组织病理学观察。 结果 超声影像学结果显示术后 2、4、8 周主动脉血流压力均显著性增加。 术后 2 周主要表现为特征性左室壁代偿性厚度增加、内径减少,收缩功能代偿性增加,但伴随舒张功能受损和心肌纤维化;术后 4 周为过渡期,主要表现为从室壁肥厚到心室扩张的过渡、收缩功能开始下降、舒张功能持续性受损、心肌进一步纤维化;术后 8 周为表现为特征性的心室腔扩大,收缩、舒张功能均显著性降低,心肌细胞部分溶解并且显著性纤维化。 结论 通过评价小鼠主动脉弓缩窄后代偿性心肌肥厚期、过渡期到失代偿扩张型心衰等三个阶段的左室结构和功能,为主动脉弓缩窄模型的在基础和转化研究上的应用提供理论依据。

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    Objective To establish a heart failure model in mice, and to use ultrasound imaging and pathology techniques to comprehensively evaluate the characteristics of cardiac function and structural changes during disease development. Methods The transverse aortic constriction ( TAC) surgical technique was used to establish a model of pressure-overload-induced heart failure in mice. Blood flow Doppler spectra were collected to evaluate the pressure at the aortic arch stenosis before surgery and at weeks 2, 4, and 8 after it. B-mode and M-mode ultrasound images were collected to evaluate cardiac structure and systolic function. The blood flow Doppler spectrum from the mitral valve orifice and tissue Doppler spectrum from the mitral annulus were combined to evaluate cardiac diastolic function, and cardiac tissues were collected for histopathological observation. Results The ultrasound result showed that the blood pressure of the aortic arch stenosis increased significantly at weeks 2, 4, and 8 after the operation. At 2 weeks after the operation, the thickness of the left ventricular wall typically showed compensatory increases, while the inner diameter was decreased, accompanied by impaired diastolic function and myocardial fibrosis. Four weeks after the operation was the transition period, which was mainly manifested as a transition of the left ventricle from hypertrophy to dilation, decreased systolic function, continuously impaired diastolic function, and further fibrosis in the myocardium. Eight weeks after surgery, the ventricle was characterized by cavity enlargement, significant reductions of systolic and diastolic function, and cardiomyocytes being partially lysed and significantly fibrotic. Conclusions By evaluating the structure and function of the left ventricle in the three stages of compensated hypertrophy, transitional stage, and decompensated dilatation of a TAC-induced heart failure model in mice, the use of the model should advance basic research and translational medicine.

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谭伟江,李想,郑双,马俊峰,任学聪,贺天真,陈虹华,陈建新,杨丰华.压力超负荷心衰小鼠模型的心脏结构和功能 病理进程特征[J].中国实验动物学报,2020,28(5):583~591.

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  • 收稿日期:2020-04-22
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  • 在线发布日期: 2020-11-25
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