Nakagawa H, Watanabe K, Shuto K, Tsurufuji S
Biochem Pharmacol. 1983 Apr 1;32(7):1191-5. doi: 10.1016/0006-2952(83)90270-8.
Proteinase inhibitors were evaluated for their anti-inflammatory actions on carrageenin-induced inflammation in rats. The development of granulation tissue and the exudate were markedly suppressed by a single injection of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK) into the carrageenin-air-pouch immediately after carrageenin injection, whereas a single injection of TPCK at 12 or 24 hr after carrageenin injection was less effective or slightly effective respectively. These results suggest that proteinase inhibitors exert their anti-inflammatory actions by interfering with the initial inflammatory reactions after carrageenin injection. When the wet weight of granulation tissue and the weight of exudate were measured on day 4 after the simultaneous injection of carrageenin and inhibitors, a single injection of serine- and thiol-proteinase inhibitors including TPCK, leupeptin, antipain, chymostatin and cystamine suppressed the development of granulation tissue, though EDTA and o-phenanthroline, metallo-proteinase inhibitors, were also effective at a high dose. Exudate was reduced by treatment with TPCK in a dose-dependent manner, while EDTA and o-phenanthroline were effective only at a high dose. On the other hand, the migration of polymorphonuclear leukocytes into the carrageenin-air-pouch (the inflammatory lesion) was markedly suppressed by TPCK and leupeptin, while a high dose of cystamine and o-phenanthroline was slightly effective, and antipain, chymostatin, pepstatin, elastatinal, EDTA, trans-1-aminomethylcyclohexane 4-carboxylic acid and aprotinin were without effect.
评估了蛋白酶抑制剂对大鼠角叉菜胶诱导的炎症的抗炎作用。在注射角叉菜胶后立即向角叉菜胶-空气囊单次注射L-1-甲苯磺酰胺-2-苯乙基氯甲基酮（TPCK），可显著抑制肉芽组织的形成和渗出物的产生，而在注射角叉菜胶后12小时或24小时单次注射TPCK，其效果分别较差或稍有效。这些结果表明，蛋白酶抑制剂通过干扰角叉菜胶注射后的初始炎症反应发挥其抗炎作用。当在同时注射角叉菜胶和抑制剂后第4天测量肉芽组织的湿重和渗出物的重量时，单次注射包括TPCK、亮抑酶肽、抗蛋白酶、抑糜酶素和胱胺在内的丝氨酸和硫醇蛋白酶抑制剂可抑制肉芽组织的形成，尽管金属蛋白酶抑制剂乙二胺四乙酸（EDTA）和邻菲罗啉在高剂量时也有效。TPCK处理可使渗出物呈剂量依赖性减少，而EDTA和邻菲罗啉仅在高剂量时有效。另一方面，TPCK和亮抑酶肽可显著抑制多形核白细胞向角叉菜胶-空气囊（炎症损伤部位）的迁移，而高剂量的胱胺和邻菲罗啉有轻微效果，抗蛋白酶、抑糜酶素、胃蛋白酶抑制剂、弹性蛋白酶抑制剂、EDTA、反式-1-氨甲基环己烷4-羧酸和抑肽酶则无效。
