Abstract

Inflammatory reaction is the crux in various clinical critical diseases including decompression sickness (DCS). Ulinastatin (UTI), a potent anti-inflammatory agent, has been used clinically, including as a substitution for steroids. This study aimed to explore the potential effects of UTI upon DCS in a rabbit model. Eighty-eight rabbits were subjected to simulated diving to 6 atmospheres absolute (ATA) for 60 min with 2.5-minute decompression. Three doses of UTI (15/7.5/3.75 × 105 U/kg) or saline were intravenously administered immediately following decompression. Circulating bubbles were monitored for 3 h following decompression and DCS signs were evaluated for 24 h. Blood was sampled 8 times during 72 h after decompression for inflammatory, endothelial, oxidative and routine blood indices. Lung tissues were also sampled for evaluating endothelial function. Another six rabbits were used as Normal controls. In the high dose UTI group the mortality, general morbidity and incidence of severe DCS was decreased from 31.25 to 9.38% (P = 0.030), 84.38 to 62.50% (P = 0.048) and 46.88 to 21.88% (P = 0.035), respectively. The high dose of UTI significantly postponed the occurrence of DCS (P = 0.030) and prolonged survival time (P = 0.009) compared with the Saline group, and significantly ameliorated inflammation responses, endothelial injuries and oxidative damage. The results strongly suggest the benefit of UTI on DCS, especially for severe cases. Large doses are needed to achieve significant effects. UTI may be a potential ideal pharmacological candidate for the treatment of severe DCS.

Highlights

  • Urinary trypsin inhibitor (Ulinastatin, UTI) is a nonspecific and multivalent Kunitz-type serine protease inhibitor purified from human urine (Yano et al, 2003)

  • Ninety-four male New Zealand White rabbits weighing 2.0∼2.3 kg were obtained from Shanghai Shengwang Laboratory Animal Co., Ltd

  • The rabbits weighted 2.16 ± 0.12 kg before simulated diving, and there was no significant difference between groups

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Summary

Introduction

Urinary trypsin inhibitor (Ulinastatin, UTI) is a nonspecific and multivalent Kunitz-type serine protease inhibitor purified from human urine (Yano et al, 2003). It is capable of suppressing various serine proteases such as trypsin, plasmin, neutrophil elastase and chymotrypsin (Nishiyama et al, 1996; Nakatani et al, 2001), and can effectively stabilize lysosomal and cellular membranes (Nakahama et al, 1999). UTI was demonstrated to exert protective effects in shock (Li et al, 2019) These clinical indications are similar to those of many steroids

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