Kawai S, Sakayori S, Watanabe H, Kobayashi H
First Department of Internal, Medicine, Kyorin University, Tokyo, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1990 Jun;28(6):843-51.
The usefulness of urinastatin (UST) for adult respiratory distress syndrome (ARDS) induced by gram-negative sepsis was evaluated in clinical and experimental studies. Twelve cases of clinical septic ARDS were treated with combination therapy of UST and methylprednisolone (M-PSL). Ten out of 12 responded favorably. This result was considered to some extent to be better than that of our previous experience with single administration of M-PSL for patients with septic ARDS. Pathophysiologic experiments on UST in endotoxic status were then performed. Immediately after the intravenous administration of endotoxin to rats, serum levels of beta-glucuronidase and elastase released from PMNs were increased and pulmonary edema was observed at 48-hours after the endotoxin injection. Various degrees of pulmonary edema were also observed by the intravenous administration of beta-glucuronidase and PMNs-elastase. These changes induced by the endotoxin were significantly inhibited by the intraperitoneal administration of UST, and they were inhibited more by the combination therapy of UST and M-PSL. In an in vitro study, significantly large amounts of beta-glucuronidase and elastase were released from PMNs by incubating human PMNs with endotoxin. By adding UST to this system, the release of these PMNs proteases was inhibited. These results suggested that UST neutralizes the PMNs-elastase release in the status endotoxemics, and consequently resulted in a better prognosis in cases of septic ARDS.
在临床和实验研究中评估了乌司他丁（UST）对革兰氏阴性菌败血症所致成人呼吸窘迫综合征（ARDS）的有效性。12例临床脓毒症性ARDS患者接受了UST与甲泼尼龙（M-PSL）的联合治疗。12例中有10例反应良好。这一结果在一定程度上被认为优于我们之前对脓毒症性ARDS患者单独使用M-PSL的经验。随后进行了内毒素状态下UST的病理生理实验。给大鼠静脉注射内毒素后，中性粒细胞释放的β-葡萄糖醛酸酶和弹性蛋白酶的血清水平立即升高，并且在内毒素注射后48小时观察到肺水肿。静脉注射β-葡萄糖醛酸酶和中性粒细胞弹性蛋白酶也观察到不同程度的肺水肿。内毒素引起的这些变化通过腹腔注射UST得到显著抑制，并且UST与M-PSL联合治疗的抑制作用更强。在一项体外研究中，通过将人中性粒细胞与内毒素孵育，中性粒细胞释放出大量的β-葡萄糖醛酸酶和弹性蛋白酶。通过向该系统中添加UST，这些中性粒细胞蛋白酶的释放受到抑制。这些结果表明，UST在内毒素血症状态下可中和中性粒细胞弹性蛋白酶的释放，从而使脓毒症性ARDS患者的预后更好。
