Mechanical Ventilation Down-Regulates Surfactant Protein A and Keratinocyte Growth Factor Expression in Premature Rabbits

Abstract

Surfactant-associated proteins (SP-A, SP-B, and SP-C) are critical for the endogenous function of surfactant. Keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF) are key regulators of lung development. The objective of this study was to evaluate the effects of early mechanical ventilation on the expression of these important regulatory proteins in a preterm rabbit model. Premature fetuses were delivered at 29 d of gestation and randomized to necropsy at birth, i.e. no ventilation (NV), spontaneous breathing (SB), or mechanical ventilation (MV) for 16 h. MV animals were further randomized to treatment with dexamethasone (dex). Our findings showed that SB rabbits increased their expression of SP-A mRNA and protein after birth compared with NV controls. MV significantly attenuated this response in the absence of dex. Exposure to dex elevated SP-B mRNA expression in both SB and MV rabbits. KGF protein levels were markedly increased in SB animals compared with MV counterparts. VEGF levels were similar in SB and MV animals, but were significantly increased compared with NV controls. These data suggest that MV alters surfactantassociated protein and growth factor expression, which may contribute to injury in the developing lung.

Effects of probiotics on ghrelin and lungs in children with acute lung injury: A double‐blind randomized, controlled trial

“…TNF‐α and IL‐6 are important inflammatory cytokines in the inflammatory cascade. Whether infective or non‐specific inflammations can elevate plasma TNF‐α and IL‐6 concentrations, which are important indicators of pulmonary and systemic inflammation . SP‐A is mainly synthesized and secreted by alveolar type II epithelial cells, and it is susceptible to changes in alveolo‐capillary barrier function.…”

Pulmonary effects of keratinocyte growth factor in newborn rats exposed to hyperoxia

“…This has potential clinical implication for BPD, since oxidative stress is a component in lung injuries leading to the occurrence of this disease in premature neonates (15). Moreover, previous investigation from our laboratory showed that in premature human neonates, high concentrations of KGF in airways were associated with low risk for BPD (17), whereas mechanical ventilation, another precipitating factor of BPD (15), was reported to downregulate KGF expression in premature rabbits (19). Last, it was shown that KGF protected premature newborn rats from hyperoxic lethality but not from hyperoxic inhibition of postnatal alveolar formation and early pulmonary fibrosis (22).…”

Mechanical stretch induces lung α-epithelial Na+channel expression

“…Oxacillin (50 mg/kg) was given intramuscularly immediately after birth to prevent infection. All animals were necropsied at 16 h of life following intrathecal injection with lidocaine, at which time whole lung tissue was isolated and snap frozen in liquid nitrogen [14].…”