Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan.
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Pediatr Res. 2019 Aug;86(2):174-180. doi: 10.1038/s41390-019-0413-9. Epub 2019 May 13.
Preclinical studies have demonstrated that maternal inflammation or neonatal hyperoxia adversely affects kidney maturation. This study explored whether prenatal lipopolysaccharide (LPS) exposure can augment neonatal hyperoxia-induced kidney injury.
Pregnant Sprague-Dawley rats received intraperitoneal injections of LPS (0.5 mg/kg) in normal saline (NS) or NS on 20 and 21 days of gestation. The pups were reared in room air (RA) or 2 weeks of 85% O, creating the four study groups, NS + RA, NS + O, LPS + RA, and LPS + O. Kidneys were taken for oxidase stress and histological analyses.
The rats exposed to maternal LPS or neonatal hyperoxia exhibited significantly higher kidney injury score, lower glomerular number, higher toll-like receptor 4 (TLR4), myeloperoxidase (MPO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expressions, and higher MPO activity compared with the rats exposed to maternal NS and neonatal RA. The rats exposed to both maternal LPS and neonatal hyperoxia exhibited significantly lower glomerular number, higher kidney injury score, TLR4, MPO, and 8-OHdG expressions compared with the rats exposed to maternal LPS or neonatal hyperoxia.
Maternal inflammation exacerbates neonatal hyperoxia-induced kidney injury and the underlying mechanism may be related to activation of TLR4 and increased oxidative stress.
临床前研究表明，母体炎症或新生儿高氧血症会对肾脏成熟产生不利影响。本研究探讨了产前脂多糖（LPS）暴露是否会加剧新生儿高氧诱导的肾脏损伤。
妊娠 Sprague-Dawley 大鼠在妊娠第 20 天和第 21 天分别接受 LPS（0.5mg/kg）生理盐水（NS）或 NS 的腹腔注射。幼鼠在空气（RA）或 85%O 中饲养 2 周，创建四个研究组，NS+RA、NS+O、LPS+RA 和 LPS+O。取肾脏进行氧化应激和组织学分析。
暴露于母体 LPS 或新生儿高氧血症的大鼠肾脏损伤评分明显升高，肾小球数量减少，Toll 样受体 4（TLR4）、髓过氧化物酶（MPO）和 8-羟基-2'-脱氧鸟苷（8-OHdG）表达增加，MPO 活性升高，与暴露于母体 NS 和新生儿 RA 的大鼠相比。同时暴露于母体 LPS 和新生儿高氧血症的大鼠肾小球数量明显减少，肾脏损伤评分、TLR4、MPO 和 8-OHdG 表达明显升高，与仅暴露于母体 LPS 或新生儿高氧血症的大鼠相比。
母体炎症加剧了新生儿高氧血症引起的肾脏损伤，其潜在机制可能与 TLR4 的激活和氧化应激增加有关。
