Protein Deprivation from the Neonatal Period Impairs Lung Development in the Rat

Abstract

ABSTRACT. The effects of early protein-deficiency on lung development were studied in the rat. Newborn male rats were nursed in groups of eight. Control dams and pups received a 15% protein diet during the whole experiment. Test mothers only received 12 and 8% proteins from the 7th and the 14th day of lactation. Test rats fed a diet of 8% protein were weaned at 21 days and maintained on the low protein diet for 1 month. This caused a marked decrease in body weight gain, but lung/body weight ratio was not affected. Lung DNA and protein content, lung protein concentration, but not lung DNA concentration were decreased, suggesting the presence of fewer and smaller cells than in control lungs. Volume-pressure curves were performed on excised lungs. With air-filling, the curve obtained in rats fed a diet with 8% proteins was shifted downward and to the right, even when expressed as percent of maximal volume. Its exponential analysis assessed a decrease in lung compliance. In contrast, with saline-filling, the recoil pressure was decreased in rats fed a diet with 8% proteins. Both with air and saline-filling, the pressure at lung rupture was increased in malnourished rats. It is concluded that protein-deficiency from the neonatal period increases surface forces, decreases tissue elastic forces, and augments resistance of the lung to rupture. (Pediatr Res 21: 45-49,1987) Abbreviations V-P, volume-pressure (P 15) rats, rats fed a diet with 15% proteins (P 8) rats, rats fed a diet with 8% proteins VHI>, volume at the point of lung rupture PHI', pressure at the point of lung rupture V30, air volume at a pressure of 30 cm H 2 0 Vlo, saline volume at a pressure of 10 cm HzO third stage (between 13 and 20 days) corresponds to elastin accumulation. The fourth stage (between 20 and 40 days) is a period of equilibrated growth in which alveolar proliferation slows and surface area increases with lung volume. The functional changes occumng during this lung maturation have been characterized recently (6).The purpose of this work was to study the influence of early protein deficiency on the development of lung mechanical properties. To this end, dams were fed a diet containing decreasing amounts of proteins during the 3 wk of lactation, and the offspring was thereafter maintained on the low protein-diet for another 4 wk. V-P curves and resistance to rupture were established with air or saline on excised lungs. Protein and DNA content of the tissue were also measured. MATERIALS AND METHODSThe control diet contained 15% proteins (15% casein, 4 1.2% starch, 13.8% glucose, 17% cellulose, 5% corn oil, and 8% vitamins and minerals). Test diets contained 12 or 8% proteins, but their carbohydrate content was increased to keep them isocaloric.Pathogen-free male Wistar rats were obtained on the first postnatal day and nursed in groups of eight. Control mothers were fed the 15% protein diet for the 3 wk of lactation, and the control offspring (P 15) were thereafter maintained on that same control diet. Test mothers received a diet with 15...

Effects of Protein Deprivation from the Neonatal Period on Lung Collagen and Elastin in the Rat

“…Lungs of rats fed on a diet restricted in protein from the neonatal period had decreased recoil pressure (6), whereas protein restriction from d 28 resulted in a moderately increased recoil pressure (7). Inasmuch as we know from the observations of Myers et al (8) rats produces an increase in lung elastin concentration, our second experiment could lend support to their conclusions.…”

“…We had previously observed that proteindeficient rats, although fed ad libitum with an isocaloric diet, reduced their food intake so that their calorie consumption was about 30% less than that of the controls; their protein intake was reduced by 65% (6). Thus the anomalies observed in the present study might result from a mixed protein-energy deficiency with a predominant protein deficit similar to the most common form of malnutrition of children in developing countries.…”

“…Lung wt, protein, and DNA content values have been discussed previously (6) and are shown to facilitate interpretation of the results.…”

“…Animals, diet compositions, mechanical procedures, and methods for tissue homogenization have been described in a previous study (6). Briefly, pathogen-free male Wistar rats were obtained on the 1st postnatal day and nursed in litters of eight.…”

“…The assays were performed on the same lung homogenates and results were analyzed in relation to lung wt, DNA and total protein content, and to mechanical findings previously described (6).…”