Jennette J C, Tidwell R R, Geratz J D, Bing D H, Falk R J
Am J Pathol. 1987 Jun;127(3):499-506.
Proteases are involved in the pathogenesis of inflammatory diseases by participating in the activation of mediator systems and by producing proteolytic tissue injury. Homeostatic control of inflammation is accomplished in part by physiologic protease inhibitors. The authors investigated the effectiveness of a number of synthetic protease inhibitors in ameliorating the glomerular injury induced by immune complex-mediated glomerulonephritis in mice. Two amidine-type protease inhibitors, bis (5-amidino-2-benzimidazolyl)methane and 1,2-bis (5-amidino-2-benzimidazolyl)ethane, had the greatest effects. They caused a marked reduction in glomerular necrosis (P less than 0.001) but did not affect the amount or site of immune complex localization or leukocyte influx. The inhibition constants of the protease inhibitors against nine purified physiologic proteases were determined. These results were discussed in relation to the effectiveness of the protease inhibitors in reducing glomerular injury. This investigation indicates that the administration of synthetic protease inhibitors can have a beneficial effect on immune-mediated inflammatory injury.
蛋白酶通过参与介质系统的激活和造成蛋白水解性组织损伤，在炎症性疾病的发病机制中发挥作用。炎症的稳态控制部分是由生理性蛋白酶抑制剂来实现的。作者研究了多种合成蛋白酶抑制剂在减轻小鼠免疫复合物介导的肾小球肾炎所致肾小球损伤方面的有效性。两种脒基型蛋白酶抑制剂，双（5-脒基-2-苯并咪唑基）甲烷和1,2-双（5-脒基-2-苯并咪唑基）乙烷，效果最为显著。它们使肾小球坏死明显减少（P小于0.001），但不影响免疫复合物定位的数量或部位以及白细胞浸润。测定了蛋白酶抑制剂对九种纯化的生理性蛋白酶的抑制常数。结合蛋白酶抑制剂在减轻肾小球损伤方面的有效性对这些结果进行了讨论。这项研究表明，给予合成蛋白酶抑制剂对免疫介导的炎症损伤可能具有有益作用。
