Mechanisms of hyperventilation-induced lung injuries in neonatal rats.
BACKGROUND
The aim of this study was to investigate the mechanism of early inflammatory injury in neonatal ventilator-induced lung injuries (VILI).


METHODS
Newborn rats were randomly assigned to groups and administrated mechanical ventilation with different tidal volumes. Morphological changes in lung tissues were observed, and the levels of interleukin-6 (IL-6), cysteinyl leukotriene mRNA (CysLT1 mRNA), and nuclear factor-κB mRNA (NF-κBp65 mRNA) in lung tissues were analyzed.


RESULTS
The ventilation groups exhibited different degrees of inflammatory cell infiltration, which was aggravated as the tidal volume and ventilation time increased. The IL-6 levels of the hyperventilation 5H, conventional ventilation 5H, hyperventilation 3H, control, and normal lung-tissue group were 785.33±39.06, 701.6±33.65, 686.65±46.85, 637.63±40.55, and 635.02±65.78 pg/g, respectively. Hyperventilation increased the levels of IL-6 and NF-κBp65 mRNA as the ventilation time increased, and IL-6 was positively correlated with NF-κBp65 mRNA levels (r=0.72, P<0.01). Longer hyperventilation periods upregulate the level of CysLT1 mRNA. CysLT1 mRNA/GAPDH of the hyperventilation 5H group was 2.14±1.45 (P<0.01).


CONCLUSIONS
Mechanical ventilation with a large tidal volume can cause VILI, characterized at an early stage by inflammatory responses and particularly by the increased secretion and invasion of inflammatory cytokines and inflammatory cells. The activation of the NF-κB-IL-6 signaling pathway was an important mechanism for the initiation of VILI. Additionally, CysLT1 was involved in the inflammatory VILI damage, and its upregulation occurred later than that of IL-6.
Department of Neonatology, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen, China.
Jinjie
J
Huang
Department of Neonatology, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen, China - wubenqing783@126.com.
Benqing
B
Wu
Department of Neonatology, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen, China.
Jinzhi
J
Song
Department of Neonatology, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen, China.
Jun
J
Wu
D000818:Animals; D000831:Animals, Newborn; D003545:Cysteine / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis; D015289:Leukotrienes / Q000235:genetics; D008168:Lung / Q000737:chemistry; D016328:NF-kappa B / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055397:Ventilator-Induced Lung Injury / Q000209:etiology* / Q000473:pathology
D015850:Interleukin-6; D015289:Leukotrienes; D016328:NF-kappa B; D012333:RNA, Messenger; C112381:cysteinyl-leukotriene; D003545:Cysteine