PDF(Pubmed)
Abstract：
Premature infants are often exposed to hyperoxia. However, there is limited data regarding the mechanistic underpinnings linking neonatal hyperoxia exposure and its contribution to cardio-renal dysfunction in adults born preterm. Our objective was to determine whether neonatal hyperoxia induces systemic vascular stiffness and cardio-renal dysfunction in adulthood. Newborn rats were randomly assigned to room air (RA) or hyperoxia (85% O2) from postnatal day 1 to 14, then recovered in RA until 1 year of life. Arterial stiffness, cardio-renal histomorphometry, and fibrosis in the aorta, heart, and kidney were assessed. RNA-sequencing (RNA-seq) of the aorta and kidney was also done. Adult rats exposed to neonatal hyperoxia had increased aortic and mesenteric artery stiffness as demonstrated by wire and pressure myography. They also had cardiomyocyte hypertrophy, glomerulomegaly, and tubular injury. Hyperoxia exposure altered the transcriptome profile associated with fibrosis and matrix remodeling in the aorta and kidney. There was also increased TGF-β1 levels and fibrosis in the aorta, left ventricle, and kidney. In conclusion, neonatal hyperoxia exposure was associated with systemic vascular and cardio-renal alterations in 1-year-old rats. Further studies to determine how targeted therapies could reprogram cardio-renal injury after neonatal hyperoxia exposure are indicated.
摘要：
早产儿经常暴露于高氧。然而,关于新生儿高氧暴露及其对早产成人心肾功能障碍的影响的机制基础的数据有限.我们的目的是确定新生儿高氧是否会在成年期引起全身血管僵硬和心肾功能障碍。从出生后的第1天到第14天，新生大鼠被随机分配到室内空气（RA）或高氧（85％O2），然后在RA中恢复，直到生命的1年。动脉僵硬度,心-肾组织形态计量学,和主动脉纤维化，心,并对肾脏进行了评估。还进行了主动脉和肾脏的RNA测序(RNA-seq)。暴露于新生儿高氧的成年大鼠的主动脉和肠系膜动脉硬度增加，如线和压力肌电图所示。他们还有心肌细胞肥大，肾小球肿大，和管状损伤。高氧暴露改变了与主动脉和肾脏纤维化和基质重塑相关的转录组概况。主动脉中TGF-β1水平和纤维化也增加，左心室,还有肾.总之,在1岁大鼠中,新生儿高氧暴露与全身血管和心-肾改变相关.指出了进一步的研究，以确定在新生儿高氧暴露后靶向治疗如何重新编程心肾损伤。
