Pulmonary surfactant に及ぼす CDP-cholineの影響に関する実験的研究

抄録

The effect of CDP-choline on the formation of pulmonary surfactant was studied histologically and biochemically. The results obtained are summarized as follows:
(1) 1,2 -¹⁴C-CDP-choline (10 μCi) was injected i ntraperitoneally into adult Sprague-Dawley rats. After 1,3,6 and 15 hours, the lungs were extirpated and subjected to histological and radioautographical studies. It was revealed that, on a carbohydrate resin section of 6-7 μthickness, the radioactive granules derived from 1,2-¹⁴C-CDP-choline were found in the alveolar epithelial cells.
(2) The pregnant rats were devided into two groups. To the first group (15rats), CDP-choline (50mg/kg/day) was administered intraperitoneally every day from the 10th gestational day onwards; the second group (20rats) had no CDP-choline administered. The parent rats were decapitated and the level of phosphatidylcholine in the fetal lungs was measured, i. e., extraction of lipids, isolation of the phosphatidylcholine by chromatography on aluminum oxide and on thin layer plates followed by determination of its phosphorus content. It was found that the phosphatidylcholine content of the CDP-choline-treated group was about 45% higher between the 19th-21st gestational days and about 15% higher between the 16th-17th days than that of the control group.
(3) A part of the fetal lungs described above was also examined by light microscopy. The tissue was fixed in glutaraldehyde and osmium tetroxide and embedded in epoxy resin. Sections (1 micronthickness) were obtained using glass knives as a Porter-Blum Sorvall MT-2 ultramicrotome. The sections were stained with toluidine blue, periodic acid-Schiff (PAS), or paraphenylene diamine. These microscopic techniques were found to be more effective than electron microscopy in observing general distribution features of the granules in the alveolar wall. Compared to the control group, the CCP-choline-treated group was demonstrated to have more inclusions in Type I I cells of the alveolar epithelium. It was also shown that this tendensy was more marked after the 19th gestational day than before the 17th day.
(4) From the results of these animal experiments, the author assumes that it would have a much marked effect on a human fetus if it were applied after the 32nd gestational week it would promote the surfactant formation and would also possibly prevent or treat the respiratory distress syndrome (RDS) at this stage