背景:这项研究旨在使用链脲佐菌素(STZ)诱导的妊娠期高血糖建立胎鼠心室致密化非(NVM)模型,并将其与视黄酸(RA)模型进行比较。
方法:雌性SD大鼠分为STZ,RA,正常对照组(NC)。STZ组孕前给予高脂饮食,孕后给予2%STZ35mg/kg。RA组在妊娠后第13天接受90mg/kg剂量的RA。通过HE染色分析胚胎心肌形态,使用电子显微镜研究了胚胎心肌细胞的超微结构。NVM的诊断基于非致密心肌(N)与致密心肌(C)的比率>1.4,伴有厚的心肌小梁和薄的心肌压实层。Kruskal-Wallis检验确定各组之间的N/C比差异。
结果:STZ组和RA组均表现出显著的NVM特征。STZ中的左心室(LV)N/C,RA,NC组为1.983(1.423-3.527),1.640(1.197-2.895),和0.927(0.806-1.087),分别,差异有统计学意义(P<0.001)。STZ中的右心室(RV)N/C,RA,NC组为2.097(1.364-3.081),1.897(1.337-2.662),和0.869(0.732-1.022),分别,有显著性差异(P<0.001)。电子显微镜显示了STZ和RA组的胚胎心肌细胞中明显的内质网肿胀。
结论:我们的模型强调了不良宫内发育环境在NVM发病中的关键作用。这一见解对探索NVM发病机制的未来研究具有重要意义。
BACKGROUND: This study aims to develop a fetal rat model of ventricular noncompaction (NVM) using streptozotocin (STZ)-induced gestational hyperglycemia and compare it with a retinoic acid (RA) model.
METHODS: Female SD rats were categorized into STZ, RA, and normal control (NC) groups. The STZ group was given a high-fat diet pre-pregnancy and 35 mg/kg of 2% STZ postpregnancy. The RA group received a 90 mg/kg dose of RA on day 13 postpregnancy. Embryonic myocardial morphology was analyzed through HE staining, and embryonic cardiomyocyte ultrastructures were studied using electron microscopy. Diagnoses of NVM were based on a ratio of noncompact myocardium (N) to compact myocardium (C) >1.4, accompanied by thick myocardial trabeculae and a thin myocardial compaction layer. Kruskal-Wallis test determined N/C ratio differences among groups.
RESULTS: Both STZ and RA groups displayed significant NVM characteristics. The left ventricular (LV) N/C in the STZ, RA, and NC groups were 1.983 (1.423-3.527), 1.640 (1.197-2.895), and 0.927 (0.806-1.087), respectively, with a statistically significant difference (P<0.001). The right ventricular (RV) N/C in the STZ, RA, and NC groups were 2.097 (1.364-3.081), 1.897 (1.337-2.662), and 0.869 (0.732-1.022), respectively, with a significant difference (P<0.001). Electron microscopy highlighted marked endoplasmic reticulum swelling in embryonic cardiomyocytes from both STZ and RA groups.
CONCLUSIONS: Our model underscores the pivotal role of an adverse intrauterine developmental environment in the onset of NVM. This insight holds significant implications for future studies exploring the pathogenesis of NVM.