Beneficial effects of ulinastatin on gut barrier function in sepsis

BACKGROUND & OBJECTIVES: The gut contains some endogenous and exogenous microorganisms that can become potential pathogens of sepsis under certain circumstances. Therefore, the integrity and normal function of gut barrier is important for preventing the development of sepsis. The present study was designed to assess the effects of ulinastatin, a urinary trypsin inhibitor on gut barrier function and mortality in experimental sepsis. METHODS: Male Sprague-Dawley rats were subjected to ceacal ligation and puncture (CLP) or sham procedure. Rats were then treated with ulinastatin 50,000 U/kg/day or saline. The mortality rate was determined. Histology, apoptosis assays, and PCR were performed using ileum specimens at 3, 6, and 12 h following CLP. Serum levels of tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) were also measured at 0, 3, 6, and 12 h following CLP. RESULTS: Compared with the saline-treated CLP rats, the ulinastatin CLP rats had significantly increased survival time (P<0.05), lower histopathological scores of intestinal injury (P<0.05), reduced apoptosis detected by terminal deoxynucleotidyl transferase dUTP nick end labelling assay and caspase 3 activity (P<0.01). Moreover, RD-5 mRNA expression was significantly higher in ulinastatin-treated CLP animals than saline controls (P<0.05). These results suggested a preserved integrity and function of the gut barrier. Significantly lower plasma TNFα and IL-6 levels were detected in CLP rats with ulinastatin treatment, which contributed to increased survival time. INTERPRETATION & CONCLUSIONS: Our results suggest that ulinastatin has a therapeutic potential to prevent gut barrier dysfunction in the early stage of sepsis, thereby improving the outcome of sepsis. Further studies need to be done to understand the mechanism of action of ulinastatin.