Department of Neonatal and Pediatric Surgery, Foshan Women and Children Hospital Affiliated to Southern Medical University, Guangdong, China.
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.
Pediatr Pulmonol. 2020 Jun;55(6):1433-1439. doi: 10.1002/ppul.24739. Epub 2020 Apr 1.
Lung hypoplasia is the main cause of congenital diaphragmatic hernia (CDH)-associated death but pathogenesis remains unclear. MiR-455-5p is involved in lung hypoplasia. We hypothesized that nitrofen causes abnormal miR-455-5p expression during lung development and designed this study to determine the relationship between miR-455-5p, stimulated by retinoic acid 6 (STRA6), and retinol in a nitrofen-induced CDH with lung hypoplasia rat model. Nitrofen or olive oil was administered to Sprague-Dawley rats by gavage on day 9.5 of gestation, and the rats were divided into a nitrofen group and a control group (n = 6). The left lung of fetuses was dissected on day 15.5. The expression of miR-455-5p or STRA6 messenger RNA (mRNA) was determined by quantitative real-time polymerase chain reaction. Average integrated optical density (IOD) of STRA6 protein was determined by immunofluorescence histochemistry. The average retinol level was detected by enzyme-linked immunosorbent assay (n = 6 lungs, respectively). Compared with the control group, the nitrofen group exhibited significantly increased miR-455-5p expression levels (29.450 ± 9.253 vs 5.955 ± 2.330; P = .00045) and significantly decreased STRA6 mRNA levels (0.197 ± 0.097 vs 0.588 ± 0.184; P = .0047). In addition, the average IOD of the STRA6 protein was significantly lower in the nitrofen group (805.643 ± 291.182 vs 1616.391 ± 572.308, P = .015), and the average retinol level was significantly reduced (4.013 ± 0.195 vs 5.317 ± 0.337 µg/L, P = .000). In summary, the overexpression of miR-455-5p affected retinol absorption by downregulating STRA6 in the nitrofen-induced CDH with lung hypoplasia rat model, and this downregulation may be one cause of CDH with lung hypoplasia.
肺发育不全是先天性膈疝（CDH）相关死亡的主要原因，但发病机制尚不清楚。miR-455-5p 参与肺发育不全。我们假设，在肺发育过程中，硝基酚会导致异常的 miR-455-5p 表达，并设计了本研究来确定在硝基酚诱导的伴有肺发育不全的 CDH 大鼠模型中，受视黄酸 6（STRA6）刺激的 miR-455-5p 与视黄醇之间的关系。在妊娠第 9.5 天，通过灌胃向 Sprague-Dawley 大鼠给予硝基酚或橄榄油，将大鼠分为硝基酚组和对照组（n=6）。在妊娠第 15.5 天解剖胎儿的左肺。通过实时定量聚合酶链反应测定 miR-455-5p 或 STRA6 信使 RNA（mRNA）的表达。通过免疫荧光组织化学测定 STRA6 蛋白的平均积分光密度（IOD）。通过酶联免疫吸附试验（n=6 个肺，分别）检测平均视黄醇水平。与对照组相比，硝基酚组 miR-455-5p 表达水平显著升高（29.450±9.253 比 5.955±2.330；P=0.00045），STRA6 mRNA 水平显著降低（0.197±0.097 比 0.588±0.184；P=0.0047）。此外，硝基酚组 STRA6 蛋白的平均 IOD 显著降低（805.643±291.182 比 1616.391±572.308，P=0.015），视黄醇水平也显著降低（4.013±0.195 比 5.317±0.337μg/L，P=0.000）。综上所述，在硝基酚诱导的伴有肺发育不全的 CDH 大鼠模型中，miR-455-5p 的过表达通过下调 STRA6 影响视黄醇的吸收，这种下调可能是 CDH 伴有肺发育不全的一个原因。
