当前位置: X-MOL 学术Lab Anim. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cauterization of the root of the left coronary artery as a straightforward, large and reproducible ischemic injury model in neonatal mice
Lab Animal ( IF 5.9 ) Pub Date : 2024-10-22 , DOI: 10.1038/s41684-024-01443-x
Tianyuan Hu, Bernd K. Fleischmann, Mona Malek Mohammadi

The adult mammalian heart is known to have very limited regenerative capacity, explaining at least in part the frequency of cardiovascular diseases and their impact as the leading cause of death worldwide. By contrast, the neonatal heart has the ability to regenerate upon injury, and the molecular mechanisms underlying this regenerative capacity are intensely investigated to provide novel cues for the repair of the adult heart. However, the existing rodent neonatal injury models—apex resection, left anterior descending artery ligation and cryoinjury—have limitations, such as being technically demanding, yielding a nonphysiological injury type and/or lack of reproducibility. Here we have therefore established a novel ischemic heart injury method in neonatal mice via cauterization of the root of the left coronary artery. This surgical procedure is technically straightforward, requires less than 10 min for completion and yields reproducible, large ischemic lesions (40% of the left ventricle) with low mortality rates (10% of animals). The injury also induces secondary pulmonary hypertension shortly after surgery, allowing to study the response of the right ventricle. Moreover, neonatal mice at postnatal days 1 and 3 display strongly opposing outcomes after the surgery, because of the lack of cardiac regeneration at the later stage. Thus, this new neonatal heart injury model is of great use for mechanistic studies exploring the regeneration of the left ventricle and the adaptation of the right ventricle upon myocardial infarction.



中文翻译:


左冠状动脉根部烧灼作为新生小鼠直接、大且可重复的缺血损伤模型



众所周知,成年哺乳动物心脏的再生能力非常有限,这至少部分解释了心血管疾病的频率及其作为全球主要死亡原因的影响。相比之下,新生儿心脏具有受伤后再生的能力,并且深入研究了这种再生能力背后的分子机制,为成人心脏的修复提供了新的线索。然而,现有的啮齿动物新生儿损伤模型(根尖切除术、左前降支结扎术和冷冻损伤)存在局限性,例如技术要求高、产生非生理性损伤类型和/或缺乏可重复性。因此,在这里,我们通过烧灼左冠状动脉根部在新生小鼠中建立了一种新的缺血性心脏病损伤方法。这种外科手术在技术上很简单,只需不到 10 分钟即可完成,并产生可重复的大缺血病变(左心室的 40%),死亡率低(动物的 10%)。该损伤还会在手术后不久诱发继发性肺动脉高压,从而可以研究右心室的反应。此外,由于后期缺乏心脏再生,出生后第 1 天和第 3 天的新生小鼠在手术后表现出强烈相反的结果。因此,这种新的新生儿心脏损伤模型对于探索左心室再生和心肌梗死后右心室适应的机制研究非常有用。

更新日期:2024-10-22
down
wechat
bug