Abstract
Defective lung septation and angiogenesis, quintessential features of neonatal chronic lung disease (CLD), typically result from lengthy exposure of developing lungs to mechanical ventilation (MV) and hyperoxia. Previous studies showed fewer alveoli and microvessels, with reduced VEGF and increased transforming growth factor-beta (TGFbeta) signaling, and excess, scattered elastin in lungs of premature infants and lambs with CLD vs. normal controls. MV of newborn mice with 40% O(2) for 24 h yielded similar lung structural abnormalities linked to impaired VEGF signaling, dysregulated elastin production, and increased apoptosis. These studies could not determine the relative importance of cyclic stretch vs. hyperoxia in causing these lung growth abnormalities. We therefore studied the impact of MV for 24 h with air on alveolar septation (quantitative lung histology), angiogenesis [CD31 quantitative-immunohistochemistry (IHC), immunoblots], apoptosis [TdT-mediated dUTP nick end labeling (TUNEL), active caspase-3 assays], VEGF signaling [VEGF-A, VEGF receptor 1 (VEGF-R1), VEGF-R2 immunoblots], TGFbeta activation [phosphorylated Smad2 (pSmad2) quantitative-IHC], and elastin production (tropoelastin immunoblots, quantitative image analysis of Hart's stained sections) in lungs of 6-day-old mice. Compared with unventilated controls, MV caused a 3-fold increase in alveolar area, approximately 50% reduction in alveolar number and endothelial surface area, >5-fold increase in apoptosis, >50% decrease in lung VEGF-R2 protein, 4-fold increase of pSmad2 protein, and >50% increase in lung elastin, which was distributed throughout alveolar walls rather than at septal tips. This study is the first to show that prolonged MV of developing lungs, without associated hyperoxia, can inhibit alveolar septation and angiogenesis and increase apoptosis and lung elastin, findings that could reflect stretch-induced changes in VEGF and TGFbeta signaling, as reported in CLD.
Highlights
Сахарный диабет (СД) является социально значимым заболеванием, т.к. отмечается значи тельная его распространенность в мире и Россий ской Федерации (РФ)
Medical examination of the newborn born from a mother type 1 diabetes mellitus (T1DM) included the assessment of glycemic profile and a full evaluation of metabolism, including lipid metabolism
The high frequency oscillatory ventilation was the possible priority in the selection of mechanical ventilation mode, which allowed to quickly eliminate hypoxia
Summary
Сахарный диабет (СД) является социально значимым заболеванием, т.к. отмечается значи тельная его распространенность в мире и Россий ской Федерации (РФ). Сахарный диабет (СД) является социально значимым заболеванием, т.к. Отмечается значи тельная его распространенность в мире и Россий ской Федерации (РФ). Динамику распространен ности СД 1 го типа в РФ можно расценить как умеренно растущее плато: +46 тысяч пациентов за 5 летний период во всех возрастных группах [1]. На этом фоне особого внимания заслуживает акушерская диабетология, т.к. У пациенток с СД все чаще наступает беременность. Беременность протекает неблагоприятно, с высо ким риском перинатальных осложнений. Гестаци онный процесс способствует развитию и прогрес сированию микрососудистых осложнений у матери. Особое внимание уделяется подбору и коррекции доз инсулина [2,3,4]
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