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Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage
Bingchang Yang1, Min Gao1, Kangkai Wang1
1Translational Medicine Center of Sepsis, Department of Pathophysiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Department of Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
Background:
Intravenous administration of ulinastatin (UTI), a broad spectral protease inhibitor, has been used on an experimental basis with severe sepsis patients in Asia. However, the effects of intraintestinal administration of UTI on intestinal and multiple organ damage in sepsis have not been reported.
Materials And Methods:
In this study, we established a sepsis model in rats using cecal ligation and puncture and compared the effects of intraintestinal administration of UTI through an artificial fistula of duodenum and intraperitoneal administration of UTI on the pathophysiological changes of sepsis.
Results:
It was found that intraintestinal administration of UTI (1) significantly improved the survival of septic rats, (2) significantly reduced the serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 as well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal microscopic and ultrastructural damage of septic rats. In addition, the protective effects of intraintestinal administration of UTI were significantly better than those of intraperitoneal administration of UTI.
Conclusions:
Overall, the present study for the first time revealed that intraintestinal administration of protease inhibitor UTI could reduce systemic inflammatory responses and multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of intestinal wall due to proteases and provided new research ideas and experimental evidences for treatment of sepsis by intraintestinal administration of UTI.
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