1987 Volume 22 Issue 6 Pages 397-407
In order to clarify the relationship between the alteration of collagen-metabolism in lungs and lung fibrosis, rats were exposed acutely and chronically to NO2, and the changes of lipid peroxides, and collagen-metabolizing factors in lungs, serum and urine were examined.
In the acute experiment with rats exposed to 10 ppm NO2 for 2 weeks, the contents of hydroxyproline in lungs and serum were significantly increased from 4 to 10 days by NO2 exposure. Collagenolytic enzyme activity in lungs at 4-10 days was higher than the control level. A significant relationship between collagenolytic enzyme activity in lungs and hydroxyproline contents in serum was observed. The activities of collagenase inhibitors in lungs and serum were decreased significantly at 1-4 days, and then the activities showed a tendency to increase over the control level from 7 to 10 days. And a significant relationship between the activities of collagenase inhibitors and the contents of lipid peroxides in lungs was observed. This result suggests that collagenase inhibitors are inactivated by lipid peroxides. Thickening of the wall of alveolar duct and ad jacent alveoli, and slight development of fibrosis were also observed microscopically at 7 and 14 days, but the degree of their changes at 14 days was less than that at 7 days. These morphological observations corresponded well with the changes of biochemical collagen-metabolizing factors in lungs, serum and urine.
In the chronic experiment with the rats exposed to 0.4, 1. 2 and 4ppm NO2 for 18 months, the dosedependent decrease of collagenolytic enzyme activity in lungs was most characteristic change. On the other hand, the activity of collagenolytic enzyme in serum was increased dose-dependently. These evidences suggest that the activity of collagenolytic enzyme in lungs might be related to that in serum, and that the decrease of collagenolytic enzyme activity in lungs might be a major mechanism of lung fibrosis observed in the morphological examination reported previously (6).
