Adjuvant関節炎ラットにおけるMucopolysaccharase, ProteaseよびCollagen分解活性の変動と諸種抗炎症剤の作用

Abstract

In adjuvant arthritic rats, the relationship between hind paw swelling and mucopolysac-charase (β-glucuronidase, N-acetyl-β-glucosaminidase and lysozyme), protease (pH 3.1 and7.0) and collagenolytic activities in serum and hind paws was investigated. Furthermore, the effects of various anti-inflammatory drugs (phenylbutazone, bucolome, indomethacin, prednisolone, azathioprine, chloroquine diphosphate and a anti-plasmin agent, DV-1006) administered orally once a day were examined 3 and 21 days after adjuvant injection. The swelling of right (injected) hind paw increased remarkably after adjuvant injection and reached a first peak on day 3, after which it decreased gradually. About 10 days later, however, it began to increase again and the swelling of left (non-injected) hind paw also occurred simultaneously. The swelling reached maximum intensity by day 21 in the right hind paw and by day 28 in the left. The activities of three mucopolysaccharases and protease at pH 3.1 in both hind paws changed as did swelling of each hind paw after adjuvant injection. Changes of these enzyme activities in serum ran parallel with those of right paw swelling. On the other hand, the collagenolytic activity in both hind paws increased rapidly and remarkably after 14 days. On day 3, swelling of the right paw was strongly inhibited by the drugs except for azathioprine, chloroquine diphosphate and DV-1006. On day 21, the swelling of both hind paws was remarkably inhibited by all drugs except chloroquine diphosphate. On day 21, a parallel relationship was proved between anti-swelling activity and anti-mucopolysaccharase or anti-protease (pH 3.1) activity in left hind paw and serum by drugs, although not necessarily on day 3. On day 21, collagenolytic activity was inhibited by all drugs. These results suggest that these lysosomal enzymes are main mediators in the development of a secondary lesion in adjuvant arthritic rats.