School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China; Sichuan Provincial Key Laboratory for Ultrasound in Cardiac Electrophysiology and Biomechanics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
Pathol Res Pract. 2019 Aug;215(8):152496. doi: 10.1016/j.prp.2019.152496. Epub 2019 Jun 10.
To develop a fetal mouse model of non-compaction of ventricular myocardium (NVM) using All-trans retinoic acid (ATRA).
Pregnant mice were divided into blank control group, dimethyl sulfoxide (DMSO) control group and ATRA group. The pregnant mice at 8.5 days after pregnancy were given 70 mg/kg ATRA in DMSO to induce fetal mouse model of NVM in ATRA group. All the hearts were acquired and sliced in short axis from the neonatal mice sacrificed after delivery. Pathological changes were visualized under 40- and 100-fold magnification with Hematoxylin-eosin (HE) staining at different ventricular levels. The criteria for pathological diagnosis of classical NVM were: prominent trabeculations on the endocardial surface and deep intertrabecular recesses communicating with the ventricular cavity and the thickness ratio of non-compacted layer (N) to compact myocardium layer (C) N/C > 1.4. Analysis of variance (ANOVA) and least significant difference (LSD) were used to analyze the differences of three groups, with P < 0.05 considered as significant.
The typical characteristics of NVM histopathological findings of ATRA fetal mouse were confirmed: compared to the hearts of blank control group (n = 20) and DMSO control group (n = 15), all the hearts of ATRA group (n = 17) showed the obviously thinner compacted layer and the much thicker non-compacted layer. The N/C ratio of left ventricles (LVs) in ATRA group was 2.735 ± 1.634, higher than those in DMSO control group 0.178 ± 0.119 and blank control group 0.195 ± 0.118 with significant difference (F = 32.550, P <0. 0001); N/C ratios of right ventricles (RVs) in the ATRA group were (6.068 ± 4.394), higher than those in the DMSO control group 0.459 ± 0.24 and in the blank control group 0.248 ± 0.182 with significant difference (F = 20.069, P <0.0001). LSD of LVs and RVs showed a significant difference between ATRA and blank control group (P < 0.0001), and between ATRA and DMSO control group (P < 0.0001). LSD showed no significant difference in two control groups of LVs (P = 0.963) and of RVs (P = 0.848) .
Excess ATRA could be used to induce NVM of fetal mice heart. This animal model might provide a platform for fundamental research of NVM pathogenesis and potential targeting treatment.
使用全反式视黄酸（ATRA）建立非致密化心肌（NVM）的胎儿小鼠模型。
将妊娠小鼠分为空白对照组、二甲基亚砜（DMSO）对照组和 ATRA 组。在妊娠第 8.5 天，ATRA 组的妊娠小鼠给予 70mg/kg ATRA 在 DMSO 中诱导 NVM 胎儿小鼠模型。从分娩后处死的新生小鼠中获取并在短轴上从心脏切片。在不同的心室水平，使用苏木精-伊红（HE）染色在 40 倍和 100 倍放大倍数下观察病理变化。经典 NVM 的病理诊断标准为：心内膜表面有明显的小梁，深小梁间陷窝与心室腔相通，非致密层（N）与致密心肌层（C）的厚度比 N/C>1.4。采用方差分析（ANOVA）和最小显著差异（LSD）分析三组间的差异，P<0.05 为差异有统计学意义。
确认 ATRA 胎儿小鼠的 NVM 组织病理学发现具有典型特征：与空白对照组（n=20）和 DMSO 对照组（n=15）相比，ATRA 组（n=17）的所有心脏均显示出明显变薄的致密层和明显增厚的非致密层。ATRA 组左心室（LV）的 N/C 比值为 2.735±1.634，高于 DMSO 对照组 0.178±0.119 和空白对照组 0.195±0.118，差异有统计学意义（F=32.550，P<0.0001）；ATRA 组右心室（RV）的 N/C 比值为（6.068±4.394），高于 DMSO 对照组 0.459±0.24 和空白对照组 0.248±0.182，差异有统计学意义（F=20.069，P<0.0001）。LSD 显示 ATRA 组与空白对照组（P<0.0001）和 ATRA 组与 DMSO 对照组（P<0.0001）之间的 LV 和 RV 差异均有统计学意义。LSD 显示两组 LV（P=0.963）和 RV（P=0.848）的差异无统计学意义。
过量 ATRA 可用于诱导胎儿小鼠心脏 NVM。该动物模型可能为 NVM 发病机制的基础研究和潜在的靶向治疗提供平台。
