TREATMENT OF SEPTIC SHOCK WITH A PROTEASE INHIBITOR IN A CANINE MODEL - A PROSPECTIVE, RANDOMIZED, CONTROLLED TRIAL
TREATMENT OF SEPTIC SHOCK WITH A PROTEASE INHIBITOR IN A CANINE MODEL - A PROSPECTIVE, RANDOMIZED, CONTROLLED TRIAL
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DOI：
10.1097/00003246-199306000-00023
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发表时间：
1993-06-01
影响因子：
8.8
通讯作者：
KODAMA, M
中科院分区：
文献类型：
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作者：
TANI, T;AOKI, H;KODAMA, M
目的：评价蛋白酶抑制剂乌司他丁治疗感染性休克的疗效及作用机制。设计：前瞻性、随机、对照试验。大学实验室。实验对象：12只杂种狗。其中一种蛋白酶抑制剂，乌司他丁，一种糖蛋白（分子量为67,000道尔顿）在人尿中检测到。我们利用大肠杆菌获得了犬脓毒性休克模型的体内研究。人中性粒细胞作为体外激活靶点。结果：大肠杆菌终浓度为1.9 × 10(6)个菌落形成单位/mL。乌司他丁处理组与对照组之间大肠杆菌浓度无显著差异。用100 U/mL乌司他丁处理的人中性粒细胞的超氧化物产量比未处理的中性粒细胞高70.5% ~ 78.7%。乌司他丁呈剂量依赖性增强吞噬活性。在乌司他丁浓度为100 U/mL时，发现其活性大约增加了两倍。乌司他丁治疗组在给药60 min后心脏指数、血压、乳酸、血糖、血碱值均明显改善，细菌计数明显减少，而对照组内毒素浓度呈持续升高的趋势。在治疗开始后60分钟观察到的监测因素的改善在治疗结束后持续存在。乌司他丁治疗组1周生存率为84%（6只狗中有5只存活），对照组1周生存率为16%（6只狗中有1只存活）（p = 0.04）。结论：乌司他丁不具有抗菌活性，不能充分激活吞噬细胞。提示该药对实验性感染性休克的疗效是由于其激活网状内皮系统和脓毒性反应的机制。
Objectives: To evaluate the efficacy and mechanism of action of a protease inhibitor (ulinastatin) in septic shock.Design: Prospective, randomized, controlled trial.Setting. A university laboratory.Subjects: Twelve mongrel dogs.Interventions. One of the protease inhibitors, ulinastatin, a glycoprotein (molecular weight 67,000 daltons) detected in human urine was estimated. We used Escherichia coli to obtain a model of septic shock in dogs in vivo study. Human neutrophils were used as an activating target in vitro.Measurements and Main Results: The final concentration of E. coli was 1.9 x 10(6) colony-forming units/mL. There was no significant difference in E. coli concentration between ulinastatin-treated and control groups. Human neutrophils treated with 100 U/mL of ulinastatin showed 70.5 % to 78.7 % of the superoxide production or untreated neutrophils. Phagocytic activity was enhanced in a dose-dependently manner by ulinastatin. At a ulinastatin concentration of 100 U/mL, an approximate two-fold increase in activation was found. In the ulinastatin-treated group, cardiac index, blood pressure, lactic acid, blood glucose, and blood base values significantly improved 60 mins after ulinastatin administration, and the bacterial count was significantly decreased, while the endotoxin concentration in the control group showed a continuous increase of endotoxin concentration. The improvement in the monitored factors observed 60 mins after initiation of treatment persisted after the end of treatment. The survival rate after 1 wk in the ulinastatin-treated group was 84% (five of six dogs survived), while it was 16% (one of six dogs survived) in the control group (p = .04).Conclusions: Ulinastatin does not have antimicrobial activity, and it does not sufficiently activate phagocytes. It is suggested that the efficacy of this agent in experimental septic shock is due to a mechanism that activates the reticuloendothelial system and septic reactions.