Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2007
Effects of recombinant Clara cell secretory protein (rhCC10) on inflammatory-related matrix metalloproteinase activity in a preterm lamb model of neonatal respiratory distress.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Miller Thomas L, Shashikant Beth N, Pilon Aprile L, Pierce Richard A, Shaffer Thomas H, Wolfson Marla R
Аннотация
OBJECTIVE: To test the hypothesis that recombinant Clara cell secretory protein (rhCC10) instillation would foster improved lung function, acute structural preservation, and attenuation of matrix metalloproteinase (MMP) activity in a surfactant-deficient, mechanically ventilated lung.
DESIGN: Interventional laboratory study.
SETTING: An academic medical research facility in the northeastern United States.
SUBJECTS: Sedated, ventilated premature lambs.
INTERVENTIONS: Preterm lambs (n = 18; 126 +/- 3 days gestation) were instrumented, ventilated, and treated with 100 mg/kg exogenous surfactant. Lambs were randomized to receive 0, 0.5, or 5.0 mg/kg rhCC10 (n = 6 per group) and were ventilated for 4 hrs.
MEASUREMENTS AND MAIN RESULTS: Posttreatment, lung function and cardiopulmonary stability were monitored for the ventilation period and then animals were killed for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, -7, and -9 as well as their tissue inhibitors (TIMP)-1 and -2. Ventilation efficiency and pulmonary compliance were improved in the 5.0-mg/kg rhCC10 group by 4 hrs. Lung expansion was variable in the apical regions only. MMP-2 quantity was greater in the apical than the base lung regions of rhCC10-treated groups, and rhCC10 decreased MMP-7 in the base of the lung.
CONCLUSIONS: These data suggest that improved lung function in the surfactant-treated preterm lamb following intratracheal rhCC10 may be related to the reduction of proteolytic activity of MMP-7.
DESIGN: Interventional laboratory study.
SETTING: An academic medical research facility in the northeastern United States.
SUBJECTS: Sedated, ventilated premature lambs.
INTERVENTIONS: Preterm lambs (n = 18; 126 +/- 3 days gestation) were instrumented, ventilated, and treated with 100 mg/kg exogenous surfactant. Lambs were randomized to receive 0, 0.5, or 5.0 mg/kg rhCC10 (n = 6 per group) and were ventilated for 4 hrs.
MEASUREMENTS AND MAIN RESULTS: Posttreatment, lung function and cardiopulmonary stability were monitored for the ventilation period and then animals were killed for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, -7, and -9 as well as their tissue inhibitors (TIMP)-1 and -2. Ventilation efficiency and pulmonary compliance were improved in the 5.0-mg/kg rhCC10 group by 4 hrs. Lung expansion was variable in the apical regions only. MMP-2 quantity was greater in the apical than the base lung regions of rhCC10-treated groups, and rhCC10 decreased MMP-7 in the base of the lung.
CONCLUSIONS: These data suggest that improved lung function in the surfactant-treated preterm lamb following intratracheal rhCC10 may be related to the reduction of proteolytic activity of MMP-7.
Предметные рубрики MeSH
AnimalsAnimals, NewbornDisease Models, AnimalEnzyme InhibitorsHumansInfant, NewbornLungLung ComplianceMetalloproteasesProtease InhibitorsPulmonary AlveoliPulmonary SurfactantsRespiration, ArtificialRespiratory Distress Syndrome, NewbornSheepTime FactorsTissue Inhibitor of Metalloproteinase-1Tissue Inhibitor of Metalloproteinase-2Treatment OutcomeUteroglobin