Cui Qing, Sun Sijuan, Zhu Hongbin, Xiao Yingying, Jiang Chuan, Zhang Hao, Liu Jinfen, Ye Lincai, Shen Jie
Department of Cardiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Pediatric Intensive Care Unit, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Cardiovasc Med. 2021 Nov 16;8:772336. doi: 10.3389/fcvm.2021.772336. eCollection 2021.
Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV remodeling may bring new insights into the post-surgical management of pediatric TOF. We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 1 (P1) using a rat model to induce neonatal VO. Echocardiography revealed that the velocity and velocity- time-integral of the pulmonary artery (PA) were significantly elevated, and hematoxylin and eosin (H&E) staining showed that the diameter of the RV significantly increased. RNA-seq analysis of the RV on P7 indicated that the top 10 enriched Gene Ontology (GO) terms and the top 20 enriched terms in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were associated with immune responses. Flow-cytometric analysis demonstrated that the number of CD4+and CD8+ immune cells were significantly augmented in the VO group compared with the sham group. A neonatal cardiac VO rat model on P1 was successfully created, providing a platform for studying the molecular biology of neonatal RV under the influence of VO. VO - induces an immune response at the neonatal stage (from P1 to P7), suggesting that immune responses may be an initiating factor for neonatal RV remodeling under the influence of VO and that immunosuppressants may be used to prevent pediatric RV remodeling caused by VO.
法洛四联症（TOF）患儿矫正或姑息手术后引起的肺动脉反流会导致慢性右心室（RV）容量超负荷（VO），进而引发青少年RV功能障碍。更好地理解VO引发新生儿RV重塑的分子机制，可能会为小儿TOF的术后管理带来新的见解。我们在出生后第1天（P1）使用大鼠模型在腹主动脉和下腔静脉之间创建瘘管，以诱导新生儿VO。超声心动图显示肺动脉（PA）的速度和速度时间积分显著升高，苏木精和伊红（H&E）染色显示RV直径显著增加。对P7时的RV进行RNA测序分析表明，基因本体论（GO）分析中前10个富集术语和京都基因与基因组百科全书（KEGG）通路分析中前20个富集术语与免疫反应相关。流式细胞术分析表明，与假手术组相比，VO组中CD4+和CD8+免疫细胞的数量显著增加。成功创建了P1时的新生儿心脏VO大鼠模型，为研究VO影响下新生儿RV的分子生物学提供了一个平台。VO在新生儿期（从P1到P7）诱导免疫反应，这表明免疫反应可能是VO影响下新生儿RV重塑的起始因素，免疫抑制剂可能用于预防VO引起的小儿RV重塑。
