Bei Yihua, Chen Chen, Hua Xuejiao, Yin Mingming, Meng Xiangmin, Huang Zhenzhen, Qi Weitong, Su Zhuhua, Liu Chang, Lehmann H Immo, Li Guoping, Huang Yu, Xiao Junjie
Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.
Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China.
NPJ Regen Med. 2023 Feb 18;8(1):9. doi: 10.1038/s41536-023-00284-5.
Neonatal mouse heart can regenerate after left ventricle (LV) apical resection (AR). Since current AR rodent method is accomplished by resecting LV apex until exposure of LV chamber, it is relatively difficult to operate reproducibly. We aimed to develop a modified AR method with high accuracy and reproducibility and to investigate whether cardiac regenerative capacity could be replicated in neonatal rats. For 15% AR of whole heart weight in 1-day-old (P1) neonatal mice, a modified 10 μL pipette tip cut to 0.48 mm in internal diameter was connected to a vacuum pump working at 0.06 ± 0.005 MPa and gently kept in touch with LV apex for nearly but no more than 12 s. LV apex was resected by a single incision adjacent to the pipette tip. The modified AR method in P1 mice achieved cardiac structural and functional recovery at 21 days post resection (dpr). Data from different operators showed smaller variation of resected LV apex and higher reproducibility using the modified AR method. Furthermore, we showed that 5% AR of whole heart weight in P1 neonatal rats using a modified 200 μL pipette tip cut to 0.63 mm in internal diameter led to complete regeneration of LV apex and full preservation of cardiac function at 42 dpr. In conclusion, the modified AR rodent model leads to accurate resection of LV apex with high homogeneity and reproducibility and it is practically convenient for the study of structural, functional, and molecular mechanisms of cardiac regeneration in both neonatal mice and rats.
新生小鼠心脏在左心室（LV）心尖切除（AR）后能够再生。由于目前啮齿动物的AR方法是通过切除LV心尖直至暴露LV腔来完成的，因此要实现可重复操作相对困难。我们旨在开发一种具有高精度和可重复性的改良AR方法，并研究是否能在新生大鼠中复制心脏再生能力。对于1日龄（P1）新生小鼠，若要切除全心脏重量的15%，将内径切割至0.48 mm的改良10 μL移液管尖端连接到以0.06±0.005 MPa工作的真空泵上，并使其与LV心尖轻轻接触近12 s，但不超过12 s。在移液管尖端附近通过单次切口切除LV心尖。P1小鼠的改良AR方法在切除后21天（dpr）实现了心脏结构和功能的恢复。来自不同操作者的数据表明，使用改良AR方法切除的LV心尖变化较小，具有更高的可重复性。此外，我们还表明，使用内径切割至0.63 mm的改良200 μL移液管尖端对P1新生大鼠进行全心脏重量5%的AR，在42 dpr时可使LV心尖完全再生并充分保留心脏功能。总之，改良的AR啮齿动物模型能够精确切除LV心尖，具有高度的同质性和可重复性，并且对于研究新生小鼠和大鼠心脏再生的结构、功能和分子机制在实际操作中很方便。
