水内 知子 東京都老人総合研究所, 基礎病理部, 研究員
水内 厚 東京都老人総合研究所, 基礎病理部, 研究員
久保井 礼 東京都老人総合研究所, 基礎病理部, 研究員
平塚 知子 東京都老人総合研究所, 基礎病理部, 研究員
KUBOI Satoshi Tokyo Metropolitan Center of Gerontology, Department of Experimental Medicine, R
MIZUUCHI Atsushi Tokyo Metropolitan Center of Gerontology, Department of Experimental Medicine, R
MIZUUCHI Tomoko Tokyo Metorpolitan Center of Gerontology, Department of Experimental Medicine, R
HIRATSUKA Tomoko Tokyo Metropolitan Center of Gerontology, Department of Experimental Medicine, R
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1989 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Present study was aimed to elucidate following :
1) Both of biochemical and morphological studies of early changes of compensatory lung growth following pneumonectomy on rats.
2) Effects of age which may contribute to change of compensatory lung growth.
3) Local difference of response in the compensatory lung growth.
Two different experiments were performed :
Experiment 1 : Fisher-344, male rats of 4 week-old, were divided two groups : Pneumonectomy group (PN group) : left pneumonectomy was performed. Sham operated group (SH group) : left chest was opened similar to PN group, but pneumonectomy was not performed. Morphological study including light morphometry and scanning electron microscopic observation and biochemical studies were performed.
Experiment 2 : Sprague-Dawley, male rats of 2 week-old, were divided similar to Experiment 1 and the same morphological and biological studied were performed.
In the results of Experiment 1 the wet weight of the contralateral lungs of the pneuminectomiz
ed rats reached the same level as both lungs of the untreated and sham-operated rats 14 days after operation. DNA polymerase activity, thymidine kinase activity and ^3H-thymidine incoroporation into DNA were measured DNA polymerase activity in the extracts of the contralateral lungs from pneumonectomized rats showed 2 peaks and was elevated on days, 1, 2, and 7. Changes in thymidine kinase activity showed similar changes but was elevate on days 1, 3, and 7. Phosphocellulose column chromatography showed a large peak of DNA polymerase alpha activity. The activity in the lung extracts of pneumonectomized rats was higher than in lung extracts of sham-operated rats on days 3 and 7. A second enzyme peak was due to DNA polymerase beta, and was found in the lungs of both groups. ^3H-thymidine incorporation was increased on day 3 and produced a subsequent increase in DNA content on day 7 in the contralateral lungs of the pneumonectomized rats. DNA synthesis increased in each lobe especially in the cardiac lobe. No changes in the activities of DNA polymerase, thymidine kinase, or ^1H-thymidine incorporation were observed in the untreated control rats.
From these observations we conclude that : 1) changes in DNA synthesis and the activities of related enzymes in the contralateral lung occur early in the post-pneumonectomy period, on the first day after the operation, and 2) increased DNA synthesis in all lobes of the remaining lung suggests that humoral factors affect compensatory lung growth but marked increase of ^3H-thymidine incorporation in the cardiac lobe indicates that local mechanical stimukation is as important as humoral factors in the early events.
From the observations of pneumonectomy on immature rats (Experiment 2), process of the compensation which included the lung volume, weight and lung morphometry was found similar to the case of adult rats. In addition, it was found that cardiac lobe in the contra-lateral lung showed the most active cellular proliferation compared with those other upper, lower, and middle lobes. Thus, it suggest in the compensatory lung growth, inter-lobar difference may exist. Less